Novel therapeutic strategies for treating Pseudomonas aeruginosa infection

References

• Silby MW, Winstanley C, Godfrey SA, et al.: Pseudomonas genomes: diverse and adaptable. FEMS Microbiol Rev 2011, 35:652–680.
   PubMed Web of Science ®Google Scholar
• Obritsch MD, Fish DN, MacLaren R, et al.: Nosocomial infections due to multidrug-resistant Pseudomonas aeruginosa: epidemiology and treatment options. Pharmacotherapy 2005, 25:1353–1364.
   PubMed Web of Science ®Google Scholar
• Sonmezer MC, Ertem G, Erdinc FS, et al.: Evaluation of risk factors for antibiotic resistance in patients with nosocomial infections caused by Pseudomonas aeruginosa. Can J Infect Dis Med Microbiol 2016, 2016:1321487.
   PubMed Web of Science ®Google Scholar
• Potron A, Poirel L, Nordmann P: Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: mechanisms and epidemiology. Int J Antimicrob Agents 2015, 45:568–585.
   PubMed Web of Science ®Google Scholar
• Guidelines for the prevention and control of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in health care facilities. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO.
   Google Scholar
• Chastre J, Wunderink R, Prokocimer P, et al.: Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. Crit Care Med 2008, 36:1089–1096.
   PubMed Web of Science ®Google Scholar
• Luyt CE, Aubry A, Lu Q, et al.: Imipenem, meropenem, or doripenem to treat patients with Pseudomonas aeruginosa ventilator-associated pneumonia. Antimicrob Agents Chemother 2014, 58:1372–1380.
   PubMed Web of Science ®Google Scholar
• Walkty A, Adam H, Baxter M, et al.: In vitro activity of plazomicin against 5,015 gram-negative and gram-positive clinical isolates obtained from patients in canadian hospitals as part of the CANWARD study, 2011-2012. Antimicrob Agents Chemother 2014, 58:2554–2563.
   PubMed Web of Science ®Google Scholar
• Pankuch GA, Lin G, Kubo A, et al.: Activity of ACHN-490 tested alone and in combination with other agents against Pseudomonas aeruginosa. Antimicrob Agents Chemother 2011, 55:2463–2465. doi:10.1128/AAC.01390-10
   PubMed Web of Science ®Google Scholar
• Cigana C, Bernardini F, Facchini M, et al.: Efficacy of the novel antibiotic POL7001 in Preclinical models of Pseudomonas aeruginosa Pneumonia. Antimicrob Agents Chemother 2016, 60:4991–5000.
   PubMed Web of Science ®Google Scholar
• Hogardt M, Hoboth C, Schmoldt S, et al.: Stage-specific adaptation of hypermutable Pseudomonas aeruginosa isolates during chronic pulmonary infection in patients with cystic fibrosis. J Infect Dis 2007, 195:70–80.
   PubMed Web of Science ®Google Scholar
• Hoboth C, Hoffmann R, Eichner A, et al.: Dynamics of adaptive microevolution of hypermutable Pseudomonas aeruginosa during chronic pulmonary infection in patients with cystic fibrosis. J Infect Dis 2009, 200:118–130.
   PubMed Web of Science ®Google Scholar
• Coggan KA, Wolfgang MC: Global regulatory pathways and cross-talk control Pseudomonas aeruginosa environmental lifestyle and virulence phenotype. Curr Issues Mol Biol 2012, 14:47–70.
   PubMed Web of Science ®Google Scholar
• Hogardt M, Heesemann J: Microevolution of Pseudomonas aeruginosa to a chronic pathogen of the cystic fibrosis lung. Curr Top Microbiol Immunol 2013, 358:91–118.
   PubMed Web of Science ®Google Scholar
• Huang H, Shao X, Xie Y, et al.: An integrated genomic regulatory network of virulence-related transcriptional factors in Pseudomonas aeruginosa. Nat Commun 2019, 10:2931.
   PubMed Web of Science ®Google Scholar
• Hauser AR: The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nat Rev Microbiol 2009, 7:654–665. doi:10.1038/nrmicro2199
   PubMed Web of Science ®Google Scholar
• Bonemann G, P A, Mogk A: Tubules and donuts: a type VI secretion story. Mol Microbiol 2010, 76:815–821. doi:10.1111/j.1365-2958.2010.07171.x
   PubMed Web of Science ®Google Scholar
• Ng WL, Bassler BL: Bacterial quorum-sensing network architectures. Annu Rev Genet 2009, 43:197–222.
   PubMed Web of Science ®Google Scholar
• Balasubramanian D, Schneper L, Kumari H, et al.: A dynamic and intricate regulatory network determines Pseudomonas aeruginosa virulence. Nucleic Acids Res 2013, 41:1–20.
   PubMed Web of Science ®Google Scholar
• Liang H, Deng X, Ji Q, et al.: The Pseudomonas aeruginosa global regulator VqsR directly inhibits QscR to control quorum-sensing and virulence gene expression. J Bacteriol 2012, 194:3098–3108.
   PubMed Web of Science ®Google Scholar
• Liang H, Deng X, Li X, et al.: Molecular mechanisms of master regulator VqsM mediating quorum-sensing and antibiotic resistance in Pseudomonas aeruginosa. Nucleic Acids Res 2014, 42:10307–10320. doi:10.1093/nar/gku586
   PubMed Web of Science ®Google Scholar
• Kong W, Zhao J, Kang H, et al.: ChIP-seq reveals the global regulator AlgR mediating cyclic di-GMP synthesis in Pseudomonas aeruginosa. Nucleic Acids Res 2015, 43:8268–8282.
   PubMed Web of Science ®Google Scholar
• Zhao J, Yu X, Zhu M, et al.: Structural and molecular mechanism of CdpR involved in Quorum-Sensing and bacterial virulence in Pseudomonas aeruginosa. PLoS Biol 2016, 14:e1002449.
   PubMed Web of Science ®Google Scholar
• Song Y, Yang C, Chen G, et al.: Molecular insights into the master regulator CysB-mediated bacterial virulence in Pseudomonas aeruginosa. Mol Microbiol 2019, 111:1195–1210.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zhou CM, Pu Q, et al.: Pseudomonas aeruginosa regulatory protein AnvM controls pathogenicity in anaerobic environments and impacts host defense. mBio. 2019;10(4):e01362–19.
   Google Scholar
• Shao X, Zhang X, Zhang Y, et al.: RpoN-dependent direct regulation of Quorum sensing and the Type VI secretion system in Pseudomonas aeruginosa PAO1. J Bacteriol 2018, 200(16):e00205–18.
   Web of Science ®Google Scholar
• Papaioannou E, Utari PD, Quax WJ: Choosing an appropriate infection model to study quorum sensing inhibition in Pseudomonas infections. Int J Mol Sci 2013, 14:19309–19340.
   PubMed Web of Science ®Google Scholar
• Anantharajah A, Mingeot-Leclercq MP, Van Bambeke F: Targeting the Type Three secretion system in Pseudomonas aeruginosa. Trends Pharmacol Sci 2016, 37:734–749.
   PubMed Web of Science ®Google Scholar
• Ranjbar M, Behrouz B, Norouzi F, et al.: Anti-PcrV IgY antibodies protect against Pseudomonas aeruginosa infection in both acute pneumonia and burn wound models. Mol Immunol 2019, 116:98–105.
   PubMed Web of Science ®Google Scholar
• Gao X, Mu Z, Qin B, et al.: Structure-based prototype peptides targeting the Pseudomonas aeruginosa Type VI secretion system effector as a novel antibacterial strategy. Front Cell Infect Microbiol 2017, 7:411.
   PubMed Web of Science ®Google Scholar
• Boulant T, Boudehen YM, Filloux A, et al.: Higher prevalence of PldA, a Pseudomonas aeruginosa Trans-Kingdom H2-Type VI secretion system effector, in clinical isolates responsible for acute infections and in multidrug resistant strains. Front Microbiol 2018, 9:2578. doi:10.3389/fmicb.2018.02578
   PubMed Web of Science ®Google Scholar
• Soukarieh F, Williams P, Stocks MJ, et al.: Pseudomonas aeruginosa Quorum sensing systems as drug discovery targets: current position and future perspectives. J Med Chem 2018, 61:10385–10402. doi:10.1021/acs.jmedchem.8b00540
   PubMed Web of Science ®Google Scholar
• Hurley MN, Camara M, Smyth AR: Novel approaches to the treatment of Pseudomonas aeruginosa infections in cystic fibrosis. Eur Respir J 2012, 40:1014–1023.
   PubMed Web of Science ®Google Scholar
• Chatterjee A, Cui Y, Hasegawa H, et al.: PsrA, the Pseudomonas sigma regulator, controls regulators of epiphytic fitness, quorum-sensing signals, and plant interactions in Pseudomonas syringae pv. tomato strain DC3000. Appl Environ Microbiol 2007, 73:3684–3694.
   PubMed Web of Science ®Google Scholar
• Kang Y, Nguyen DT, Son MS, et al.: The Pseudomonas aeruginosa PsrA responds to long-chain fatty acid signals to regulate the fadBA5 beta-oxidation operon. Microbiology 2008, 154:1584–1598.
   PubMed Web of Science ®Google Scholar
• Wells G, Palethorpe S, Pesci EC: PsrA controls the synthesis of the Pseudomonas aeruginosa quinolone signal via repression of the FadE homolog, PA0506. PLoS One 2017, 12:e0189331.
   PubMedGoogle Scholar
• Lizewski SE, Schurr JR, Jackson DW, et al.: Identification of AlgR-regulated genes in Pseudomonas aeruginosa by use of microarray analysis. J Bacteriol 2004, 186:5672–5684.
   PubMedGoogle Scholar
• Moradali MF, Ghods S, Rehm BH: Pseudomonas aeruginosa lifestyle: a paradigm for adaptation, survival, and persistence. Front Cell Infect Microbiol 2017, 7:39.
   PubMed Web of Science ®Google Scholar
• Chang CY: Surface sensing for biofilm formation in Pseudomonas aeruginosa. Front Microbiol 2017, 8:2671.
   PubMedGoogle Scholar
• Jimenez PN, Koch G, Thompson JA, et al.: The multiple signaling systems regulating virulence in Pseudomonas aeruginosa. Microbiol Mol Biol Rev 2012, 76:46–65.
   PubMed Web of Science ®Google Scholar
• Lee J, Wu J, Deng Y, et al.: A cell-cell communication signal integrates quorum sensing and stress response. Nat Chem Biol 2013, 9:339–343. doi:10.1038/nchembio.1225
   PubMed Web of Science ®Google Scholar
• Muhlen S, Dersch P: Anti-virulence strategies to target bacterial infections. Curr Top Microbiol Immunol 2016, 398:147–183.
   PubMed Web of Science ®Google Scholar
• Wagner S, Sommer R, Hinsberger S, et al.: Novel strategies for the treatment of Pseudomonas aeruginosa infections. J Med Chem 2016, 59:5929–5969. doi:10.1021/acs.jmedchem.5b01698
   PubMed Web of Science ®Google Scholar
• Pearson JP, Passador L, Iglewski BH, et al.: A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 1995, 92:1490–1494.
   PubMed Web of Science ®Google Scholar
• Passador L, Cook JM, Gambello MJ, et al.: Expression of Pseudomonas aeruginosa virulence genes requires cell-to-cell communication. Science 1993, 260:1127–1130. doi:10.1126/science.8493556
   PubMed Web of Science ®Google Scholar
• Wu CLY, K, X, Feng P: Benzene ring substituted N-acyl homoserine lactone compounds as well as preparation method and application thereof. 2017:CN106749119A.
   Google Scholar
• Geske GD, Wezeman RJ, Siegel AP, et al.: Small molecule inhibitors of bacterial quorum sensing and biofilm formation. J Am Chem Soc 2005, 127:12762–12763.
   PubMed Web of Science ®Google Scholar
• Persson T, Hansen TH, Rasmussen TB, et al.: Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic. Org Biomol Chem 2005, 3:253–262.
   PubMed Web of Science ®Google Scholar
• Geske GD, O’Neill JC, Miller DM, et al.: Comparative analyses of N-acylated homoserine lactones reveal unique structural features that dictate their ability to activate or inhibit quorum sensing. Chembiochem 2008, 9:389–400.
   PubMed Web of Science ®Google Scholar
• Mattmann ME, Shipway PM, Heth NJ, et al.: Potent and selective synthetic modulators of a quorum sensing repressor in Pseudomonas aeruginosa identified from second-generation libraries of N-acylated L-homoserine lactones. Chembiochem 2011, 12:942–949. doi:10.1002/cbic.201000708
   PubMed Web of Science ®Google Scholar
• Jadhav GP, Chhabra SR, Telford G, et al.: Immunosuppressive but non-LasR-inducing analogues of the Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone. J Med Chem 2011, 54:3348–3359.
   PubMed Web of Science ®Google Scholar
• Stacy DM, Le Quement ST, Hansen CL, et al.: Synthesis and biological evaluation of triazole-containing N-acyl homoserine lactones as quorum sensing modulators. Org Biomol Chem 2013, 11:938–954.
   PubMed Web of Science ®Google Scholar
• Moore JD, Rossi FM, Welsh MA, et al.: A comparative analysis of synthetic Quorum sensing modulators in Pseudomonas aeruginosa: new insights into mechanism, active efflux susceptibility, phenotypic response, and next-generation ligand design. J Am Chem Soc 2015, 137:14626–14639.
   PubMed Web of Science ®Google Scholar
• Hodgkinson JT, Galloway WR, Wright M, et al.: Design, synthesis and biological evaluation of non-natural modulators of quorum sensing in Pseudomonas aeruginosa. Org Biomol Chem 2012, 10:6032–6044.
   PubMed Web of Science ®Google Scholar
• McInnis CE, Blackwell HE: Design, synthesis, and biological evaluation of abiotic, non-lactone modulators of LuxR-type quorum sensing. Bioorg Med Chem 2011, 19:4812–4819.
   PubMedGoogle Scholar
• Park S, Kim HS, Ok K, et al.: Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors. Bioorg Med Chem Lett 2015, 25:2913–2917.
   PubMedGoogle Scholar
• Yates EA, Philipp B, Buckley C, et al.: N-acylhomoserine lactones undergo lactonolysis in a pH-, temperature-, and acyl chain length-dependent manner during growth of Yersinia pseudotuberculosis and Pseudomonas aeruginosa. Infect Immun 2002, 70:5635–5646. doi:10.1128/IAI.70.10.5635-5646.2002
   PubMed Web of Science ®Google Scholar
• Decho AW, Frey RL, Ferry JL: Chemical challenges to bacterial AHL signaling in the environment. Chem Rev 2011, 111:86–99. doi:10.1021/cr100311q
   PubMed Web of Science ®Google Scholar
• Amara N, Mashiach R, Amar D, et al.: Covalent inhibition of bacterial quorum sensing. J Am Chem Soc 2009, 131:10610–10619.
   PubMed Web of Science ®Google Scholar
• Deng X, Weerapana E, Ulanovskaya O, et al.: Proteome-wide quantification and characterization of oxidation-sensitive cysteines in pathogenic bacteria. Cell Host Microbe 2013, 13:358–370.
   PubMed Web of Science ®Google Scholar
• Amara N, Gregor R, Rayo J, et al.: Fine-tuning covalent inhibition of bacterial Quorum sensing. Chembiochem 2016, 17:825–835.
   PubMed Web of Science ®Google Scholar
• O’Brien KT, Noto JG, Nichols-O’Neill L, et al.: Potent irreversible inhibitors of LasR Quorum sensing in Pseudomonas aeruginosa. ACS Med Chem Lett 2015, 6:162–167.
   PubMed Web of Science ®Google Scholar
• Lidor O, Al-Quntar A, Pesci EC, et al.: Mechanistic analysis of a synthetic inhibitor of the Pseudomonas aeruginosa LasI quorum-sensing signal synthase. Sci Rep 2015, 5:16569.
   PubMed Web of Science ®Google Scholar
• Latifi A, Foglino M, Tanaka K, et al.: A hierarchical quorum-sensing cascade in Pseudomonas aeruginosa links the transcriptional activators LasR and RhIR (VsmR) to expression of the stationary-phase sigma factor RpoS. Mol Microbiol 1996, 21:1137–1146. doi:10.1046/j.1365-2958.1996.00063.x
   PubMed Web of Science ®Google Scholar
• Seed PC, Passador L, Iglewski BH: Activation of the Pseudomonas aeruginosa lasI gene by LasR and the Pseudomonas autoinducer PAI: an autoinduction regulatory hierarchy. J Bacteriol 1995, 177:654–659.
   PubMed Web of Science ®Google Scholar
• Blackwell HBB, M. E, Moore JD: Synthetic Ligands that modulate the activity of the rhlR Quorum sensing receptor. WO2017190116A1 2017.
   Google Scholar
• O’Loughlin CT, Miller LC, Siryaporn A, et al.: A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proc Natl Acad Sci U S A 2013, 110:17981–17986. doi:10.1073/pnas.1316981110
   PubMed Web of Science ®Google Scholar
• Eibergen NR, Moore JD, Mattmann ME, et al.: Potent and selective modulation of the RhlR Quorum sensing receptor by using non-native ligands: an emerging target for virulence control in Pseudomonas aeruginosa. Chembiochem 2015, 16:2348–2356. doi:10.1002/cbic.201500357
   PubMed Web of Science ®Google Scholar
• Ilangovan A, Fletcher M, Rampioni G, et al.: Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR). PLoS Pathog 2013, 9:e1003508.
   PubMed Web of Science ®Google Scholar
• Soukarieh F, Vico Oton E, Dubern JF, et al. Silico and in vitro-guided identification of inhibitors of Alkylquinolone-dependent Quorum sensing in Pseudomonas aeruginosa. Molecules 2018;23(2):257.
   Web of Science ®Google Scholar
• Aleksic I, Segan S, Andric F, et al.: Long-Chain 4-Aminoquinolines as Quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa. ACS Chem Biol 2017, 12:1425–1434.
   PubMed Web of Science ®Google Scholar
• Lesic B, Lepine F, Deziel E, et al.: Inhibitors of pathogen intercellular signals as selective anti-infective compounds. PLoS Pathog 2007, 3:1229–1239. doi:10.1371/journal.ppat.0030126
   PubMed Web of Science ®Google Scholar
• Kitao T, Lepine F, Babloudi S, et al. Molecular insights into function and competitive inhibition of Pseudomonas aeruginosa multiple virulence factor regulator. MBio 2018;9(1):e02158-17.
   Web of Science ®Google Scholar
• Witzgall F, Ewert W, Blankenfeldt W: Structures of the N-Terminal domain of PqsA in complex with Anthraniloyl- and 6-Fluoroanthraniloyl-AMP: substrate activation in Pseudomonas Quinolone signal (PQS) biosynthesis. Chembiochem 2017, 18:2045–2055.
   PubMed Web of Science ®Google Scholar
• Luo J, Dong B, Wang K, et al.: Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model. PLoS One 2017, 12:e0176883.
   PubMed Web of Science ®Google Scholar
• Manefield M, Rasmussen TB, Henzter M, et al.: Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover. Microbiology 2002, 148:1119–1127.
   PubMed Web of Science ®Google Scholar
• Wu H, Song Z, Hentzer M, et al.: Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice. J Antimicrob Chemother 2004, 53:1054–1061.
   PubMed Web of Science ®Google Scholar
• Rasmussen TB, Skindersoe ME, Bjarnsholt T, et al.: Identity and effects of quorum-sensing inhibitors produced by penicillium species. Microbiology 2005, 151:1325–1340.
   PubMed Web of Science ®Google Scholar
• Muh U, Hare BJ, Duerkop BA, et al.: A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal. Proc Natl Acad Sci U S A 2006, 103:16948–16952.
   PubMed Web of Science ®Google Scholar
• Kutty SK, Barraud N, Ho KK, et al.: Hybrids of acylated homoserine lactone and nitric oxide donors as inhibitors of quorum sensing and virulence factors in Pseudomonas aeruginosa. Org Biomol Chem 2015, 13:9850–9861. doi:10.1039/C5OB01373A
   PubMed Web of Science ®Google Scholar
• Smith KM, Bu Y, Suga H: Library screening for synthetic agonists and antagonists of a Pseudomonas aeruginosa autoinducer. Chem Biol 2003, 10:563–571. doi:10.1016/S1074-5521(03)00107-8
   PubMed Web of Science ®Google Scholar
• Bijtenhoorn P, Mayerhofer H, Muller-Dieckmann J, et al.: A novel metagenomic short-chain dehydrogenase/reductase attenuates Pseudomonas aeruginosa biofilm formation and virulence on Caenorhabditis elegans. PLoS One 2011, 6:e26278.
   PubMed Web of Science ®Google Scholar
• Paczkowski JE, Mukherjee S, McCready AR, et al. Pseudomonas aeruginosa virulence through allosteric inhibition of Quorum-sensing receptors. J Biol Chem 2017, 292:4064–4076.
   PubMed Web of Science ®Google Scholar
• Kim B, Park JS, Choi HY, et al.: Terrein is an inhibitor of quorum sensing and c-di-GMP in Pseudomonas aeruginosa: a connection between quorum sensing and c-di-GMP. Sci Rep 2018, 8:8617.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Sass A, Van Acker H, et al., Coenye T: coumarin reduces virulence and biofilm formation in Pseudomonas aeruginosa by affecting Quorum sensing, Type III Secretion and C-di-GMP levels. Front Microbiol 2018, 9:1952.
   PubMedGoogle Scholar
• Abbas HA, Elsherbini AM, Shaldam MA: Repurposing metformin as a quorum sensing inhibitor in Pseudomonas aeruginosa. Afr Health Sci 2017, 17:808–819.
   PubMed Web of Science ®Google Scholar
• Kalia M, Yadav VK, Singh PK, et al.: Exploring the impact of parthenolide as anti-quorum sensing and anti-biofilm agent against Pseudomonas aeruginosa. Life Sci 2018, 199:96–103.
   PubMed Web of Science ®Google Scholar
• Chatterjee M, D’Morris S, Paul V, et al.: Mechanistic understanding of Phenyllactic acid mediated inhibition of quorum sensing and biofilm development in Pseudomonas aeruginosa. Appl Microbiol Biotechnol 2017, 101:8223–8236. doi:10.1007/s00253-017-8546-4
   PubMed Web of Science ®Google Scholar
• Heidari A, Noshiranzadeh N, Haghi F, et al.: Inhibition of quorum sensing related virulence factors of Pseudomonas aeruginosa by pyridoxal lactohydrazone. Microb Pathog 2017, 112:103–110.
   PubMed Web of Science ®Google Scholar
• Thomann A, de Mello Martins AG, Brengel C, et al.: Application of dual inhibition concept within looped autoregulatory systems toward antivirulence agents against Pseudomonas aeruginosa infections. ACS Chem Biol 2016, 11:1279–1286.
   PubMed Web of Science ®Google Scholar
• Kumar L, Chhibber S, Kumar R, et al.: Zingerone silences quorum sensing and attenuates virulence of Pseudomonas aeruginosa. Fitoterapia 2015, 102:84–95. doi:10.1016/j.fitote.2015.02.002
   PubMed Web of Science ®Google Scholar
• Gokalsin B, Aksoydan B, Erman B, et al.: Reducing virulence and biofilm of Pseudomonas aeruginosa by potential Quorum sensing inhibitor carotenoid: zeaxanthin. Microb Ecol 2017, 74:466–473.
   PubMed Web of Science ®Google Scholar
• Gillis RJ, White KG, Choi KH, et al.: Molecular basis of azithromycin-resistant Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 2005, 49:3858–3867.
   PubMed Web of Science ®Google Scholar
• Hentzer M, Wu H, Andersen JB, et al.: Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. Embo J 2003, 22:3803–3815.
   PubMed Web of Science ®Google Scholar
• Fong J, Yuan M, Jakobsen TH, et al.: Disulfide bond-containing Ajoene analogues as novel Quorum sensing inhibitors of Pseudomonas aeruginosa. J Med Chem 2017, 60:215–227.
   PubMed Web of Science ®Google Scholar
• Jakobsen TH, van Gennip M, Phipps RK, et al.: Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing. Antimicrob Agents Chemother 2012, 56:2314–2325.
   PubMed Web of Science ®Google Scholar
• El-Mowafy SA, Shaaban MI, Abd E, et al.: Sodium ascorbate as a quorum sensing inhibitor of Pseudomonas aeruginosa. J Appl Microbiol 2014, 117:1388–1399.
   PubMed Web of Science ®Google Scholar
• Ishida T, Ikeda T, Takiguchi N, et al.: Inhibition of quorum sensing in Pseudomonas aeruginosa by N-acyl cyclopentylamides. Appl Environ Microbiol 2007, 73:3183–3188.
   PubMed Web of Science ®Google Scholar
• Hassan R, Shaaban MI, Abdel Bar FM, et al.: Quorum sensing inhibiting activity of streptomyces coelicoflavus isolated from soil. Front Microbiol 2016, 7:659. doi:10.3389/fmicb.2016.00659
   PubMed Web of Science ®Google Scholar
• Wang M, Zhao L, Wu H, et al. Cladodionen is a potential Quorum sensing inhibitor against Pseudomonas aeruginosa. Mar Drugs 2020;18(4):205.
   Web of Science ®Google Scholar
• Rasmussen TB, Bjarnsholt T, Skindersoe ME, et al.: Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector. J Bacteriol 2005, 187:1799–1814.
   PubMed Web of Science ®Google Scholar
• Cady NC, McKean KA, Behnke J, et al.: Inhibition of biofilm formation, quorum sensing and infection in Pseudomonas aeruginosa by natural products-inspired organosulfur compounds. PLoS One 2012, 7:e38492.
   PubMed Web of Science ®Google Scholar
• Muh U, Schuster M, Heim R, et al.: Novel Pseudomonas aeruginosa quorum-sensing inhibitors identified in an ultra-high-throughput screen. Antimicrob Agents Chemother 2006, 50:3674–3679.
   PubMed Web of Science ®Google Scholar
• Musthafa KS, Balamurugan K, Pandian SK, et al.: 2,5-Piperazinedione inhibits quorum sensing-dependent factor production in Pseudomonas aeruginosa PAO1. J Basic Microbiol 2012, 52:679–686. doi:10.1002/jobm.201100292
   PubMed Web of Science ®Google Scholar
• El-Mowafy SA, Abd E, Galil KH, et al.: Aspirin is an efficient inhibitor of quorum sensing, virulence and toxins in Pseudomonas aeruginosa. Microb Pathog 2014, 74:25–32.
   PubMed Web of Science ®Google Scholar
• Maura D, Rahme LG: Pharmacological inhibition of the Pseudomonas aeruginosa MvfR Quorum-sensing system interferes with biofilm formation and potentiates antibiotic-mediated biofilm disruption. Antimicrob Agents Chemother 2017;61(12):e01362-17.
   Web of Science ®Google Scholar
• Soukarieh F, Liu R, Romero M, et al.: Hit identification of new potent PqsR antagonists as inhibitors of Quorum sensing in Planktonic and biofilm grown Pseudomonas aeruginosa. Front Chem 2020, 8:204.
   PubMed Web of Science ®Google Scholar
• Calfee MW, Coleman JP, Pesci EC: Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 2001, 98:11633–11637.
   PubMed Web of Science ®Google Scholar
• Coleman JP, Hudson LL, McKnight SL, et al.: Pseudomonas aeruginosa PqsA is an anthranilate-coenzyme A ligase. J Bacteriol 2008, 190:1247–1255.
   PubMedGoogle Scholar
• Ji C, Sharma I, Pratihar D, et al.: Designed small-molecule inhibitors of the Anthranilyl-CoA synthetase PqsA block Quinolone biosynthesis in Pseudomonas aeruginosa. ACS Chem Biol 2019, 14:1380. doi:10.1021/acschembio.9b00298
   PubMed Web of Science ®Google Scholar
• Hinsberger S, de Jong JC, Groh M, et al.: Benzamidobenzoic acids as potent PqsD inhibitors for the treatment of Pseudomonas aeruginosa infections. Eur J Med Chem 2014, 76:343–351.
   PubMed Web of Science ®Google Scholar
• Weidel E, de Jong JC, Brengel C, et al.: Structure optimization of 2-benzamidobenzoic acids as PqsD inhibitors for Pseudomonas aeruginosa infections and elucidation of binding mode by SPR, STD NMR, and molecular docking. J Med Chem 2013, 56:6146–6155.
   PubMed Web of Science ®Google Scholar
• Zhou Z, Ma S: Recent Advances in the Discovery of PqsD Inhibitors as Antimicrobial Agents. ChemMedChem 2017, 12:420–425.
   PubMed Web of Science ®Google Scholar
• Drees SL, Li C, Prasetya F, et al.: PqsBC, a condensing enzyme in the biosynthesis of the Pseudomonas aeruginosa Quinolone signal: crystal structure, inhibition, and reaction mechanism. J Biol Chem 2016, 291:6610–6624. doi:10.1074/jbc.M115.708453
   PubMed Web of Science ®Google Scholar
• Valastyan JS, Tota MR, Taylor IR, et al.: Discovery of PqsE Thioesterase inhibitors for Pseudomonas aeruginosa using DNA-encoded small molecule library screening. ACS Chem Biol 2020, 15:446–456.
   PubMed Web of Science ®Google Scholar
• Baldelli V, D’Angelo F, Pavoncello V, et al.: Identification of FDA-approved antivirulence drugs targeting the Pseudomonas aeruginosa quorum sensing effector protein PqsE. Virulence 2020, 11:652–668.
   PubMedGoogle Scholar
• Akisoglu O, Engin D, Saricam S, et al.: [Multilocus sequence analysis, biofilm production, antibiotic susceptibility and synergy tests of Burkholderia species in patients with and without cystic fibrosis]. Mikrobiyol Bul 2019, 53:22–36.
   PubMed Web of Science ®Google Scholar
• Kaushik KS, Stolhandske J, Shindell O, et al.: Tobramycin and bicarbonate synergise to kill planktonic Pseudomonas aeruginosa, but antagonise to promote biofilm survival. NPJ Biofilms Microbiomes 2016, 2:16006. doi:10.1038/npjbiofilms.2016.6
   PubMed Web of Science ®Google Scholar
• Aanaes K, Eickhardt S, Johansen HK, et al.: Sinus biofilms in patients with cystic fibrosis: is adjusted eradication therapy needed? Eur Arch Otorhinolaryngol 2015, 272:2291–2297. doi:10.1007/s00405-014-3322-x
   PubMed Web of Science ®Google Scholar
• Stewart PS, Franklin MJ: Physiological heterogeneity in biofilms. Nat Rev Microbiol 2008, 6:199–210.
   PubMed Web of Science ®Google Scholar
• Beitelshees M, Hill A, Jones CH, et al.: Phenotypic variation during biofilm formation: implications for anti-biofilm therapeutic design. Materials (Basel) 2018;11(7):1086.
   Web of Science ®Google Scholar
• Simm R, Morr M, Kader A, et al.: GGDEF and EAL domains inversely regulate cyclic di-GMP levels and transition from sessility to motility. Mol Microbiol 2004, 53:1123–1134.
   PubMed Web of Science ®Google Scholar
• Ha DG, O’Toole GA: c-di-GMP and its effects on biofilm formation and dispersion: a Pseudomonas aeruginosa review. Microbiol Spectr 2015, 3:MB-0003-2014. doi:10.1128/microbiolspec.MB-0003-2014
   PubMed Web of Science ®Google Scholar
• Flemming HC, Wingender J: The biofilm matrix. Nat Rev Microbiol 2010, 8:623–633.
   PubMed Web of Science ®Google Scholar
• Billings N, Millan M, Caldara M, et al.: The extracellular matrix component Psl provides fast-acting antibiotic defense in Pseudomonas aeruginosa biofilms. PLoS Pathog 2013, 9:e1003526.
   PubMed Web of Science ®Google Scholar
• Pedersen SS, Espersen F, Hoiby N, et al.: Purification, characterization, and immunological cross-reactivity of alginates produced by mucoid Pseudomonas aeruginosa from patients with cystic fibrosis. J Clin Microbiol 1989, 27:691–699.
   PubMed Web of Science ®Google Scholar
• Smith EE, Buckley DG, Wu Z, et al.: Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci U S A 2006, 103:8487–8492. doi:10.1073/pnas.0602138103
   PubMed Web of Science ®Google Scholar
• Wozniak DJ, Wyckoff TJ, Starkey M, et al.: Alginate is not a significant component of the extracellular polysaccharide matrix of PA14 and PAO1 Pseudomonas aeruginosa biofilms. Proc Natl Acad Sci U S A 2003, 100:7907–7912. doi:10.1073/pnas.1231792100
   PubMed Web of Science ®Google Scholar
• Colvin KM, Gordon VD, Murakami K, et al.: The pel polysaccharide can serve a structural and protective role in the biofilm matrix of Pseudomonas aeruginosa. PLoS Pathog 2011, 7:e1001264. doi:10.1371/journal.ppat.1001264
   PubMed Web of Science ®Google Scholar
• Yang L, Hu Y, Liu Y, et al.: Distinct roles of extracellular polymeric substances in Pseudomonas aeruginosa biofilm development. Environ Microbiol 2011, 13:1705–1717.
   PubMed Web of Science ®Google Scholar
• Friedman L, Kolter R: Genes involved in matrix formation in Pseudomonas aeruginosa PA14 biofilms. Mol Microbiol 2004, 51:675–690.
   PubMed Web of Science ®Google Scholar
• Friedman L, Kolter R: Two genetic loci produce distinct carbohydrate-rich structural components of the Pseudomonas aeruginosa biofilm matrix. J Bacteriol 2004, 186:4457–4465. doi:10.1128/JB.186.14.4457-4465.2004
   PubMed Web of Science ®Google Scholar
• Ma L, Conover M, Lu H, et al.: Assembly and development of the Pseudomonas aeruginosa biofilm matrix. PLoS Pathog 2009, 5:e1000354.
   PubMed Web of Science ®Google Scholar
• Byrd MS, Sadovskaya I, Vinogradov E, et al.: Genetic and biochemical analyses of the Pseudomonas aeruginosa Psl exopolysaccharide reveal overlapping roles for polysaccharide synthesis enzymes in Psl and LPS production. Mol Microbiol 2009, 73:622–638.
   PubMed Web of Science ®Google Scholar
• Yu S, Su T, Wu H, et al.: PslG, a self-produced glycosyl hydrolase, triggers biofilm disassembly by disrupting exopolysaccharide matrix. Cell Res 2015, 25:1352–1367.
   PubMed Web of Science ®Google Scholar
• Barraud N, Hassett DJ, Hwang SH, et al.: Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa. J Bacteriol 2006, 188:7344–7353.
   PubMed Web of Science ®Google Scholar
• Barraud N, Kelso MJ, Rice SA, et al.: Nitric oxide: a key mediator of biofilm dispersal with applications in infectious diseases. Curr Pharm Des 2015, 21:31–42. doi:10.2174/1381612820666140905112822
   PubMed Web of Science ®Google Scholar
• Cathie K, H R, Carroll M, et al. G385 RATNO – reducing antibiotic tolerance using nitric oxide in cystic fibrosis: report of a proof of concept clinical trial. Arch Dis Child. 2014;99:A159.
   Google Scholar
• Yepuri NR, Barraud N, Mohammadi NS, et al.: Synthesis of cephalosporin-3ʹ-diazeniumdiolates: biofilm dispersing NO-donor prodrugs activated by beta-lactamase. Chem Commun (Camb) 2013, 49:4791–4793. doi:10.1039/c3cc40869h
   PubMed Web of Science ®Google Scholar
• Hentzer M, Riedel K, Rasmussen TB, et al.: Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 2002, 148:87–102. doi:10.1099/00221287-148-1-87
   PubMed Web of Science ®Google Scholar
• Chang Y, Wang PC, Ma HM, et al.: Design, synthesis and evaluation of halogenated furanone derivatives as quorum sensing inhibitors in Pseudomonas aeruginosa. Eur J Pharm Sci 2019, 140:105058. doi:10.1016/j.ejps.2019.105058
   PubMed Web of Science ®Google Scholar
• Nizalapur S, Kimyon O, Yee E, et al.: Synthesis and biological evaluation of novel acyclic and cyclic glyoxamide based derivatives as bacterial quorum sensing and biofilm inhibitors. Org Biomol Chem 2017, 15:5743–5755.
   PubMed Web of Science ®Google Scholar
• Yang L, Rybtke MT, Jakobsen TH, et al.: Computer-aided identification of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors. Antimicrob Agents Chemother 2009, 53:2432–2443. doi:10.1128/AAC.01283-08
   PubMed Web of Science ®Google Scholar
• Srinivasarao S, Nandikolla A, Nizalapur S, et al. Design, synthesis and biological evaluation of 1,2,3-triazole based 2-aminobenzimidazoles as novel inhibitors of LasR dependent quorum sensing in Pseudomonas aeruginosa. RSC Adv 2019, 9:29273–29292.
   Web of Science ®Google Scholar
• Moreau-Marquis S, O’Toole GA, Stanton BA: Tobramycin and FDA-approved iron chelators eliminate Pseudomonas aeruginosa biofilms on cystic fibrosis cells. Am J Respir Cell Mol Biol 2009, 41:305–313.
   PubMed Web of Science ®Google Scholar
• Minandri F, Bonchi C, Frangipani E, et al.: Promises and failures of gallium as an antibacterial agent. Future Microbiol 2014, 9:379–397.
   PubMed Web of Science ®Google Scholar
• Kaneko Y, Thoendel M, Olakanmi O, et al.: The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity. J Clin Invest 2007, 117:877–888.
   PubMed Web of Science ®Google Scholar
• Chronopoulou L, Amalfitano A, Palocci C, et al.: Dexamethasone-loaded biopolymeric nanoparticles promote gingival fibroblasts differentiation. Biotechnol Prog 2015, 31:1381–1387.
   PubMed Web of Science ®Google Scholar
• Cifani N, Chronopoulou L, Pompili B, et al.: Improved stability and efficacy of chitosan/pDNA complexes for gene delivery. Biotechnol Lett 2015, 37:557–565.
   PubMed Web of Science ®Google Scholar
• Peulen TO, Wilkinson KJ: Diffusion of nanoparticles in a biofilm. Environ Sci Technol 2011, 45:3367–3373.
   PubMed Web of Science ®Google Scholar
• Li X, Yeh YC, Giri K, et al.: Control of nanoparticle penetration into biofilms through surface design. Chem Commun (Camb) 2015, 51:282–285. doi:10.1039/C4CC07737G
   PubMed Web of Science ®Google Scholar
• Chatterjee M, Anju CP, Biswas L, et al.: Antibiotic resistance in Pseudomonas aeruginosa and alternative therapeutic options. Int J Med Microbiol 2016, 306:48–58. doi:10.1016/j.ijmm.2015.11.004
   PubMed Web of Science ®Google Scholar
• Baelo A, Levato R, Julian E, et al.: Disassembling bacterial extracellular matrix with DNase-coated nanoparticles to enhance antibiotic delivery in biofilm infections. J Control Release 2015, 209:150–158.
   PubMed Web of Science ®Google Scholar
• Gunday Tureli N, Torge A, Juntke J, et al.: Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections. Eur J Pharm Biopharm 2017, 117:363–371.
   PubMed Web of Science ®Google Scholar
• Wang L, Hu C, Shao L: The antimicrobial activity of nanoparticles: present situation and prospects for the future. Int J Nanomedicine 2017, 12:1227–1249.
   PubMed Web of Science ®Google Scholar
• Brown AN, Smith K, Samuels TA, et al.: Nanoparticles functionalized with ampicillin destroy multiple-antibiotic-resistant isolates of Pseudomonas aeruginosa and Enterobacter aerogenes and methicillin-resistant Staphylococcus aureus. Appl Environ Microbiol 2012, 78:2768–2774.
   PubMed Web of Science ®Google Scholar
• Annamalai A, Christina VL, Sudha D, et al.: Green synthesis, characterization and antimicrobial activity of Au NPs using Euphorbia hirta L. leaf extract. Colloids Surf B Biointerfaces 2013, 108:60–65.
   PubMed Web of Science ®Google Scholar
• Jamil B, Habib H, Abbasi S, et al.: Cefazolin loaded chitosan nanoparticles to cure multi drug resistant Gram-negative pathogens. Carbohydr Polym 2016, 136:682–691. doi:10.1016/j.carbpol.2015.09.078
   PubMed Web of Science ®Google Scholar
• Elsaesser A, Howard CV: Toxicology of nanoparticles. Adv Drug Deliv Rev 2012, 64:129–137. doi:10.1016/j.addr.2011.09.001
   PubMed Web of Science ®Google Scholar
• Inoue K, Takano H, Yanagisawa R, et al.: Effects of airway exposure to nanoparticles on lung inflammation induced by bacterial endotoxin in mice. Environ Health Perspect 2006, 114:1325–1330.
   PubMed Web of Science ®Google Scholar
• Miller MR, Raftis JB, Langrish JP, et al.: Inhaled nanoparticles accumulate at sites of vascular disease. ACS Nano 2017, 11:4542–4552.
   PubMed Web of Science ®Google Scholar
• Marks LR, Davidson BA, Knight PR, et al.: Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease. mBio 2013;4(4):e00438-13.
   Web of Science ®Google Scholar
• Rollet C, Gal L, Guzzo J: Biofilm-detached cells, a transition from a sessile to a planktonic phenotype: a comparative study of adhesion and physiological characteristics in Pseudomonas aeruginosa. FEMS Microbiol Lett 2009, 290:135–142. doi:10.1111/j.1574-6968.2008.01415.x
   PubMed Web of Science ®Google Scholar
• Lewis K: Persister cells, dormancy and infectious disease. Nat Rev Microbiol 2007, 5:48–56.
   PubMed Web of Science ®Google Scholar
• Yamazaki A, Li J, Zeng Q, et al.: Derivatives of plant phenolic compound affect the type III secretion system of Pseudomonas aeruginosa via a GacS-GacA two-component signal transduction system. Antimicrob Agents Chemother 2012, 56:36–43.
   PubMed Web of Science ®Google Scholar
• Grier MC, Garrity-Ryan LK, Bartlett VJ, et al.: N-Hydroxybenzimidazole inhibitors of ExsA MAR transcription factor in Pseudomonas aeruginosa: in vitro anti-virulence activity and metabolic stability. Bioorg Med Chem Lett 2010, 20:3380–3383.
   PubMed Web of Science ®Google Scholar
• Marsden AE, King JM, Spies MA, et al.: Inhibition of Pseudomonas aeruginosa ExsA DNA-binding activity by N-Hydroxybenzimidazoles. Antimicrob Agents Chemother 2016, 60:766–776.
   PubMed Web of Science ®Google Scholar
• Felise HB, Nguyen HV, Pfuetzner RA, et al.: An inhibitor of gram-negative bacterial virulence protein secretion. Cell Host Microbe 2008, 4:325–336.
   PubMed Web of Science ®Google Scholar
• Kline T, Barry KC, Jackson SR, et al.: Tethered thiazolidinone dimers as inhibitors of the bacterial type III secretion system. Bioorg Med Chem Lett 2009, 19:1340–1343.
   PubMed Web of Science ®Google Scholar
• Aiello D, Williams JD, Majgier-Baranowska H, et al.: Discovery and characterization of inhibitors of Pseudomonas aeruginosa type III secretion. Antimicrob Agents Chemother 2010, 54:1988–1999.
   PubMed Web of Science ®Google Scholar
• Bowlin NO, Williams JD, Knoten CA, et al.: Mutations in the Pseudomonas aeruginosa needle protein gene pscF confer resistance to phenoxyacetamide inhibitors of the type III secretion system. Antimicrob Agents Chemother 2014, 58:2211–2220.
   PubMed Web of Science ®Google Scholar
• Williams JD, Torhan MC, Neelagiri VR, et al.: Synthesis and structure-activity relationships of novel phenoxyacetamide inhibitors of the Pseudomonas aeruginosa type III secretion system (T3SS). Bioorg Med Chem 2015, 23:1027–1043.
   PubMed Web of Science ®Google Scholar
• Sawa T, Yahr TL, Ohara M, et al.: Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury. Nat Med 1999, 5:392–398.
   PubMed Web of Science ®Google Scholar
• Frank DW, Vallis A, Wiener-Kronish JP, et al.: Generation and characterization of a protective monoclonal antibody to Pseudomonas aeruginosa PcrV. J Infect Dis 2002, 186:64–73. doi:10.1086/341069
   PubMed Web of Science ®Google Scholar
• Lynch SV, Flanagan JL, Sawa T, et al.: Polymorphisms in the Pseudomonas aeruginosa type III secretion protein, PcrV - implications for anti-PcrV immunotherapy. Microb Pathog 2010, 48:197–204.
   PubMed Web of Science ®Google Scholar
• Imamura Y, Yanagihara K, Fukuda Y, et al.: Effect of anti-PcrV antibody in a murine chronic airway Pseudomonas aeruginosa infection model. Eur Respir J 2007, 29:965–968.
   PubMed Web of Science ®Google Scholar
• Thaden JT, Keller AE, Shire NJ, et al.: Pseudomonas aeruginosa bacteremic patients exhibit nonprotective antibody titers against therapeutic antibody targets PcrV and Psl Exopolysaccharide. J Infect Dis 2016, 213:640–648.
   PubMed Web of Science ®Google Scholar
• DiGiandomenico A, Keller AE, Gao C, et al.: A multifunctional bispecific antibody protects against Pseudomonas aeruginosa. Sci Transl Med 2014, 6:262ra155.
   PubMed Web of Science ®Google Scholar
• Arnoldo A, Curak J, Kittanakom S, et al.: Identification of small molecule inhibitors of Pseudomonas aeruginosa exoenzyme S using a yeast phenotypic screen. PLoS Genet 2008, 4:e1000005.
   PubMed Web of Science ®Google Scholar
• Lee VT, Pukatzki S, Sato H, et al.: Pseudolipasin A is a specific inhibitor for phospholipase A2 activity of Pseudomonas aeruginosa cytotoxin ExoU. Infect Immun 2007, 75:1089–1098.
   PubMed Web of Science ®Google Scholar
• Kim D, Baek J, Song J, et al.: Identification of arylsulfonamides as ExoU inhibitors. Bioorg Med Chem Lett 2014, 24:3823–3825. doi:10.1016/j.bmcl.2014.06.064
   PubMed Web of Science ®Google Scholar
• Faure E, Mear JB, Faure K, et al.: Pseudomonas aeruginosa type-3 secretion system dampens host defense by exploiting the NLRC4-coupled inflammasome. Am J Respir Crit Care Med 2014, 189:799–811. doi:10.1164/rccm.201307-1358OC
   PubMed Web of Science ®Google Scholar
• Cohen TS, Prince AS: Activation of inflammasome signaling mediates pathology of acute P. aeruginosa pneumonia. J Clin Invest 2013, 123:1630–1637.
   PubMed Web of Science ®Google Scholar
• Wu W, Huang J, Duan B, et al.: Th17-stimulating protein vaccines confer protection against Pseudomonas aeruginosa pneumonia. Am J Respir Crit Care Med 2012, 186:420–427.
   PubMed Web of Science ®Google Scholar
• Barbieri JT, Sun J: Pseudomonas aeruginosa ExoS and ExoT. Rev Physiol Biochem Pharmacol 2004, 152:79–92.
   PubMed Web of Science ®Google Scholar
• Anantharajah A, Buyck JM, Sundin C, et al. Hydroxyquinolines act as inhibitors of Type Three secretion systems in Pseudomonas aeruginosa by distinct mechanisms. Antimicrob Agents Chemother. 2017;61(6):e02566-16.
   Web of Science ®Google Scholar
• Shen DK, Filopon D, Kuhn L, et al.: PsrA is a positive transcriptional regulator of the type III secretion system in Pseudomonas aeruginosa. Infect Immun 2006, 74:1121–1129. doi:10.1128/IAI.74.2.1121-1129.2006
   PubMed Web of Science ®Google Scholar
• Akeda Y, Galan JE: Chaperone release and unfolding of substrates in type III secretion. Nature 2005, 437:911–915.
   PubMed Web of Science ®Google Scholar
• Brutinel ED, Vakulskas CA, Brady KM, et al.: Characterization of ExsA and of ExsA-dependent promoters required for expression of the Pseudomonas aeruginosa type III secretion system. Mol Microbiol 2008, 68:657–671. doi:10.1111/j.1365-2958.2008.06179.x
   PubMed Web of Science ®Google Scholar
• Vakulskas CA, Brady KM, Yahr TL: Mechanism of transcriptional activation by Pseudomonas aeruginosa ExsA. J Bacteriol 2009, 191:6654–6664.
   PubMed Web of Science ®Google Scholar
• Brutinel ED, Vakulskas CA, Yahr TL: ExsD inhibits expression of the Pseudomonas aeruginosa type III secretion system by disrupting ExsA self-association and DNA binding activity. J Bacteriol 2010, 192:1479–1486.
   PubMed Web of Science ®Google Scholar
• Marsden AE, Intile PJ, Schulmeyer KH, et al.: Vfr directly activates exsA transcription to regulate expression of the Pseudomonas aeruginosa Type III secretion system. J Bacteriol 2016, 198:1442–1450. doi:10.1128/JB.00049-16
   PubMed Web of Science ®Google Scholar
• Brutinel ED, Vakulskas CA, Yahr TL: Functional domains of ExsA, the transcriptional activator of the Pseudomonas aeruginosa type III secretion system. J Bacteriol 2009, 191:3811–3821. doi:10.1128/JB.00002-09
   PubMed Web of Science ®Google Scholar
• Diaz MR, King JM, Yahr TL: Intrinsic and extrinsic regulation of Type III secretion gene expression in Pseudomonas aeruginosa. Front Microbiol 2011, 2:89.
   PubMed Web of Science ®Google Scholar
• Intile PJ, Balzer GJ, Wolfgang MC, et al.: The RNA Helicase DeaD stimulates ExsA translation to promote expression of the Pseudomonas aeruginosa Type III secretion system. J Bacteriol 2015, 197:2664–2674.
   PubMed Web of Science ®Google Scholar
• Jovanovic M, Lilic M, Savic DJ, et al.: The LysR-type transcriptional regulator CysB controls the repression of hslJ transcription in Escherichia coli. Microbiology 2003, 149:3449–3459.
   PubMed Web of Science ®Google Scholar
• Ren D, Zuo R, Gonzalez Barrios AF, et al.: Differential gene expression for investigation of Escherichia coli biofilm inhibition by plant extract ursolic acid. Appl Environ Microbiol 2005, 71:4022–4034. doi:10.1128/AEM.71.7.4022-4034.2005
   PubMed Web of Science ®Google Scholar
• Delic-Attree I, Toussaint B, Garin J, et al.: Cloning, sequence and mutagenesis of the structural gene of Pseudomonas aeruginosa CysB, which can activate algD transcription. Mol Microbiol 1997, 24:1275–1284.
   PubMed Web of Science ®Google Scholar
• Imperi F, Tiburzi F, Fimia GM, et al.: Transcriptional control of the pvdS iron starvation sigma factor gene by the master regulator of sulfur metabolism CysB in Pseudomonas aeruginosa. Environ Microbiol 2010, 12:1630–1642. doi:10.1111/j.1462-2920.2010.02210.x
   PubMed Web of Science ®Google Scholar
• Farrow JM 3rd, Hudson LL, Wells G, et al.: CysB negatively affects the transcription of pqsR and Pseudomonas Quinolone signal production in Pseudomonas aeruginosa. J Bacteriol 2015, 197:1988–2002.
   PubMed Web of Science ®Google Scholar
• Mougous JD, Cuff ME, Raunser S, et al.: A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 2006, 312:1526–1530. doi:10.1126/science.1128393
   PubMed Web of Science ®Google Scholar
• Rahme LG, Stevens EJ, Wolfort SF, et al.: Common virulence factors for bacterial pathogenicity in plants and animals. Science 1995, 268:1899–1902.
   PubMed Web of Science ®Google Scholar
• Rahme LG, Ausubel FM, Cao H, et al.: Plants and animals share functionally common bacterial virulence factors. Proc Natl Acad Sci U S A 2000, 97:8815–8821.
   PubMed Web of Science ®Google Scholar
• Waligora EA, Ramsey DM, Pryor EE Jr., et al.: AmrZ beta-sheet residues are essential for DNA binding and transcriptional control of Pseudomonas aeruginosa virulence genes. J Bacteriol 2010, 192:5390–5401. doi:10.1128/JB.00711-10
   PubMed Web of Science ®Google Scholar
• Hendrickson EL, Plotnikova J, Mahajan-Miklos S, et al.: Differential roles of the Pseudomonas aeruginosa PA14 rpoN gene in pathogenicity in plants, nematodes, insects, and mice. J Bacteriol 2001, 183:7126–7134.
   PubMedGoogle Scholar
• Mulcahy H, O’Callaghan J, O’Grady EP, et al.: Pseudomonas aeruginosa RsmA plays an important role during murine infection by influencing colonization, virulence, persistence, and pulmonary inflammation. Infect Immun 2008, 76:632–638.
   PubMed Web of Science ®Google Scholar
• Romero M, Silistre H, Lovelock L, et al.: Genome-wide mapping of the RNA targets of the Pseudomonas aeruginosa riboregulatory protein RsmN. Nucleic Acids Res 2018, 46:6823–6840. doi:10.1093/nar/gky324
   PubMed Web of Science ®Google Scholar
• Hall CW, Zhang L, Mah TF. PA3225 is a transcriptional repressor of antibiotic resistance mechanisms in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2017;61(8):e02114-16.
   Web of Science ®Google Scholar
• Lizewski SE, Lundberg DS, Schurr MJ: The transcriptional regulator AlgR is essential for Pseudomonas aeruginosa pathogenesis. Infect Immun 2002, 70:6083–6093. doi:10.1128/IAI.70.11.6083-6093.2002
   PubMed Web of Science ®Google Scholar
• Juhas M, Wiehlmann L, Huber B, et al.: Global regulation of quorum sensing and virulence by VqsR in Pseudomonas aeruginosa. Microbiology 2004, 150:831–841.
   PubMed Web of Science ®Google Scholar
• Yeung AT, Torfs EC, Jamshidi F, et al.: Swarming of Pseudomonas aeruginosa is controlled by a broad spectrum of transcriptional regulators, including MetR. J Bacteriol 2009, 191:5592–5602.
   PubMed Web of Science ®Google Scholar
• Deretic V, Dikshit R, Konyecsni WM, et al.: The algR gene, which regulates mucoidy in Pseudomonas aeruginosa, belongs to a class of environmentally responsive genes. J Bacteriol 1989, 171:1278–1283.
   PubMed Web of Science ®Google Scholar
• Whitchurch CB, Alm RA, Mattick JS: The alginate regulator AlgR and an associated sensor FimS are required for twitching motility in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 1996, 93:9839–9843.
   PubMed Web of Science ®Google Scholar
• Okkotsu Y, Tieku P, Fitzsimmons LF, et al.: Pseudomonas aeruginosa AlgR phosphorylation modulates rhamnolipid production and motility. J Bacteriol 2013, 195:5499–5515. doi:10.1128/JB.00726-13
   PubMed Web of Science ®Google Scholar
• Marko VA, Kilmury SLN, MacNeil LT, et al.: Pseudomonas aeruginosa type IV minor pilins and PilY1 regulate virulence by modulating FimS-AlgR activity. PLoS Pathog 2018, 14:e1007074.
   PubMed Web of Science ®Google Scholar
• Stacey SD, Williams DA, Pritchett CL. The Pseudomonas aeruginosa Two-Component Regulator AlgR directly activates rsmA expression in a phosphorylation-independent manner. J Bacteriol.  2017;199(18):e00048-17.
   Web of Science ®Google Scholar
• Dong YH, Zhang XF, Xu JL, et al.: VqsM, a novel AraC-type global regulator of quorum-sensing signalling and virulence in Pseudomonas aeruginosa. Mol Microbiol 2005, 58:552–564.
   PubMed Web of Science ®Google Scholar
• Vatansever F, de Melo WC, Avci P, et al.: Antimicrobial strategies centered around reactive oxygen species–bactericidal antibiotics, photodynamic therapy, and beyond. FEMS Microbiol Rev 2013, 37:955–989.
   PubMed Web of Science ®Google Scholar
• Robinson JM: Phagocytic leukocytes and reactive oxygen species. Histochem Cell Biol 2009, 131:465–469.
   PubMed Web of Science ®Google Scholar
• Robinson JM: Reactive oxygen species in phagocytic leukocytes. Histochem Cell Biol 2008, 130:281–297. doi:10.1007/s00418-008-0461-4
   PubMed Web of Science ®Google Scholar
• Malhotra S, Hayes D, Wozniak DJ Jr.: Cystic fibrosis and Pseudomonas aeruginosa: the host-microbe interface. Clin Microbiol Rev. 2019;32(3):e00138-18.
   Web of Science ®Google Scholar
• Chen PR, Brugarolas P, He C: Redox signaling in human pathogens. Antioxid Redox Signal 2011, 14:1107–1118.
   PubMed Web of Science ®Google Scholar
• Kim SO, Merchant K, Nudelman R, et al.: OxyR: a molecular code for redox-related signaling. Cell 2002, 109:383–396.
   PubMed Web of Science ®Google Scholar
• Fuangthong M, Helmann JD: The OhrR repressor senses organic hydroperoxides by reversible formation of a cysteine-sulfenic acid derivative. Proc Natl Acad Sci U S A 2002, 99:6690–6695.
   PubMed Web of Science ®Google Scholar
• Zimmermann A, Reimmann C, Galimand M, et al.: Anaerobic growth and cyanide synthesis of Pseudomonas aeruginosa depend on anr, a regulatory gene homologous with fnr of Escherichia coli. Mol Microbiol 1991, 5:1483–1490.
   PubMed Web of Science ®Google Scholar
• Cai Z, Liu Y, Chen Y, et al.: RpoN regulates virulence factors of Pseudomonas aeruginosa via modulating the PqsR quorum sensing regulator. Int J Mol Sci 2015, 16:28311–28319.
   PubMed Web of Science ®Google Scholar
• Heurlier K, Denervaud V, Pessi G, et al.: Negative control of quorum sensing by RpoN (sigma54) in Pseudomonas aeruginosa PAO1. J Bacteriol 2003, 185:2227–2235. doi:10.1128/JB.185.7.2227-2235.2003
   PubMed Web of Science ®Google Scholar
• Thompson LS, Webb JS, Rice SA, et al.: The alternative sigma factor RpoN regulates the quorum sensing gene rhlI in Pseudomonas aeruginosa. FEMS Microbiol Lett 2003, 220:187–195. doi:10.1016/S0378-1097(03)00097-1
   PubMed Web of Science ®Google Scholar
• Caiazza NC, O’Toole GA: SadB is required for the transition from reversible to irreversible attachment during biofilm formation by Pseudomonas aeruginosa PA14. J Bacteriol 2004, 186:4476–4485.
   PubMed Web of Science ®Google Scholar
• Sana TG, Soscia C, Tonglet CM, et al.: Divergent control of Two Type VI secretion systems by RpoN in Pseudomonas aeruginosa. PLoS One 2013, 8:e76030.
   PubMedGoogle Scholar
• Dasgupta N, Wolfgang MC, Goodman AL, et al.: A four-tiered transcriptional regulatory circuit controls flagellar biogenesis in Pseudomonas aeruginosa. Mol Microbiol 2003, 50:809–824. doi:10.1046/j.1365-2958.2003.03740.x
   PubMed Web of Science ®Google Scholar
• Ishimoto KS, Lory S: Formation of pilin in Pseudomonas aeruginosa requires the alternative sigma factor (RpoN) of RNA polymerase. Proc Natl Acad Sci U S A 1989, 86:1954–1957.
   PubMed Web of Science ®Google Scholar
• Semmler AB, Whitchurch CB, Mattick JS: A re-examination of twitching motility in Pseudomonas aeruginosa. Microbiology 1999, 145 (Pt 10):2863–2873.
   PubMedGoogle Scholar
• Kohler T, Harayama S, Ramos JL, et al.: Involvement of Pseudomonas putida RpoN sigma factor in regulation of various metabolic functions. J Bacteriol 1989, 171:4326–4333.
   PubMed Web of Science ®Google Scholar
• Herrera MC, Duque E, Rodriguez-Herva JJ, et al.: Identification and characterization of the PhhR regulon in Pseudomonas putida. Environ Microbiol 2010, 12:1427–1438.
   PubMed Web of Science ®Google Scholar
• Viducic D, Murakami K, Amoh T, et al.: RpoN promotes Pseudomonas aeruginosa Survival in the Presence of tobramycin. Front Microbiol 2017, 8:839.
   PubMedGoogle Scholar
• Viducic D, Ono T, Murakami K, et al.: rpoN gene of Pseudomonas aeruginosa alters its susceptibility to quinolones and carbapenems. Antimicrob Agents Chemother 2007, 51:1455–1462. doi:10.1128/AAC.00348-06
   PubMed Web of Science ®Google Scholar
• Viducic D, Murakami K, Amoh T, et al.: RpoN modulates Carbapenem tolerance in Pseudomonas aeruginosa through Pseudomonas Quinolone signal and PqsE. Antimicrob Agents Chemother 2016, 60:5752–5764.
   PubMed Web of Science ®Google Scholar
• Schulz S, Eckweiler D, Bielecka A, et al.: Elucidation of sigma factor-associated networks in Pseudomonas aeruginosa reveals a modular architecture with limited and function-specific crosstalk. PLoS Pathog 2015, 11:e1004744. doi:10.1371/journal.ppat.1004744
   PubMed Web of Science ®Google Scholar
• Hagins JM, Scoffield JA, Suh SJ, et al.: Influence of RpoN on isocitrate lyase activity in Pseudomonas aeruginosa. Microbiology 2010, 156:1201–1210.
   PubMed Web of Science ®Google Scholar
• Lloyd MG, Vossler JL, Nomura CT, et al.: Blocking RpoN reduces virulence of Pseudomonas aeruginosa isolated from cystic fibrosis patients and increases antibiotic sensitivity in a laboratory strain. Sci Rep 2019, 9:6677. doi:10.1038/s41598-019-43060-6
   PubMed Web of Science ®Google Scholar
• Lloyd MG, Lundgren BR, Hall CW, et al.: Targeting the alternative sigma factor RpoN to combat virulence in Pseudomonas aeruginosa. Sci Rep 2017, 7:12615.
   PubMed Web of Science ®Google Scholar
• Meyer JM, Neely A, Stintzi A, et al.: Pyoverdin is essential for virulence of Pseudomonas aeruginosa. Infect Immun 1996, 64:518–523.
   PubMed Web of Science ®Google Scholar
• Takase H, Nitanai H, Hoshino K, et al.: Impact of siderophore production on Pseudomonas aeruginosa infections in immunosuppressed mice. Infect Immun 2000, 68:1834–1839. doi:10.1128/IAI.68.4.1834-1839.2000
   PubMed Web of Science ®Google Scholar
• Imperi F, Massai F, Facchini M, et al.: Repurposing the antimycotic drug flucytosine for suppression of Pseudomonas aeruginosa pathogenicity. Proc Natl Acad Sci U S A 2013, 110:7458–7463.
   PubMed Web of Science ®Google Scholar
• Kirienko NV, Kirienko DR, Larkins-Ford J, et al.: Pseudomonas aeruginosa disrupts Caenorhabditis elegans iron homeostasis, causing a hypoxic response and death. Cell Host Microbe 2013, 13:406–416.
   PubMed Web of Science ®Google Scholar
• Lopez-Medina E, Fan D, Coughlin LA, et al.: Candida albicans inhibits Pseudomonas aeruginosa virulence through suppression of pyochelin and pyoverdine biosynthesis. PLoS Pathog 2015, 11:e1005129.
   PubMed Web of Science ®Google Scholar
• Minandri F, Imperi F, Frangipani E, et al.: Role of iron uptake systems in Pseudomonas aeruginosa virulence and airway infection. Infect Immun 2016, 84:2324–2335.
   PubMed Web of Science ®Google Scholar
• Beare PA, For RJ, Martin LW, et al.: Siderophore-mediated cell signalling in Pseudomonas aeruginosa: divergent pathways regulate virulence factor production and siderophore receptor synthesis. Mol Microbiol 2003, 47:195–207.
   PubMed Web of Science ®Google Scholar
• Ochsner UA, Johnson Z, Lamont IL, et al.: Exotoxin A production in Pseudomonas aeruginosa requires the iron-regulated pvdS gene encoding an alternative sigma factor. Mol Microbiol 1996, 21:1019–1028.
   PubMed Web of Science ®Google Scholar
• Wilderman PJ, Vasil AI, Johnson Z, et al.: Characterization of an endoprotease (PrpL) encoded by a PvdS-regulated gene in Pseudomonas aeruginosa. Infect Immun 2001, 69:5385–5394.
   PubMed Web of Science ®Google Scholar
• Lamont IL, Beare PA, Ochsner U, et al.: Siderophore-mediated signaling regulates virulence factor production in Pseudomonasaeruginosa. Proc Natl Acad Sci U S A 2002, 99:7072–7077. doi:10.1073/pnas.092016999
   PubMed Web of Science ®Google Scholar
• Takase H, Nitanai H, Hoshino K, et al.: Requirement of the Pseudomonas aeruginosa tonB gene for high-affinity iron acquisition and infection. Infect Immun 2000, 68:4498–4504. doi:10.1128/IAI.68.8.4498-4504.2000
   PubMed Web of Science ®Google Scholar
• Banin E, Vasil ML, Greenberg EP: Iron and Pseudomonas aeruginosa biofilm formation. Proc Natl Acad Sci U S A 2005, 102:11076–11081.
   PubMed Web of Science ®Google Scholar
• Costabile G, d’Angelo I, d’Emmanuele, et al.: Development of inhalable hyaluronan/mannitol composite dry powders for flucytosine repositioning in local therapy of lung infections. J Control Release 2016, 238:80–91.
   PubMed Web of Science ®Google Scholar
• Kirienko DR, Revtovich AV, Kirienko NV, et al., Phenotypic screen identifies fluorouridine as an inhibitor of pyoverdine biosynthesis and Pseudomonas aeruginosa virulence. mSphere. mSphere. 2016;1(4):e00217-16.
   Web of Science ®Google Scholar
• Kang D, Revtovich AV, Chen Q, et al.: Pyoverdine-dependent virulence of Pseudomonas aeruginosa isolates from cystic fibrosis patients. Front Microbiol 2019, 10:2048. doi:10.3389/fmicb.2019.02048
   PubMed Web of Science ®Google Scholar
• Kirienko DR, Kang D, Kirienko NV: Novel pyoverdine inhibitors mitigate Pseudomonas aeruginosa pathogenesis. Front Microbiol 2018, 9:3317. doi:10.3389/fmicb.2018.03317
   PubMed Web of Science ®Google Scholar
• Kang D, Kirienko NV: High-throughput genetic screen reveals that early attachment and biofilm formation are necessary for full pyoverdine production by Pseudomonas aeruginosa. Front Microbiol 2017, 8:1707.
   PubMed Web of Science ®Google Scholar
• Drake EJ, Gulick AM: Structural characterization and high-throughput screening of inhibitors of PvdQ, an NTN hydrolase involved in pyoverdine synthesis. ACS Chem Biol 2011, 6:1277–1286. doi:10.1021/cb2002973
   PubMed Web of Science ®Google Scholar
• Theriault JR, Wurst J, Jewett I, et al.: Identification of a small molecule inhibitor of Pseudomonas aeruginosa PvdQ acylase, an enzyme involved in siderophore pyoverdine synthesis. In Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD); 2010. Available from: http://www.ncbi.nlm.nih.gov/books/NBK133446/
   Google Scholar
• Clevenger KD, Wu R, Er JA, et al.: Rational design of a transition state analogue with picomolar affinity for Pseudomonas aeruginosa PvdQ, a siderophore biosynthetic enzyme. ACS Chem Biol 2013, 8:2192–2200. doi:10.1021/cb400345h
   PubMed Web of Science ®Google Scholar
• Wibowo JP, Batista FA, van Oosterwijk N, et al.: A novel mechanism of inhibition by phenylthiourea on PvdP, a tyrosinase synthesizing pyoverdine of Pseudomonas aeruginosa. Int J Biol Macromol 2020, 146:212–221.
   PubMed Web of Science ®Google Scholar
• Young R: Phage lysis: three steps, three choices, one outcome. J Microbiol 2014, 52:243–258.
   PubMed Web of Science ®Google Scholar
• Wittebole X, De Roock S, Opal SM: A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens. Virulence 2014, 5:226–235.
   PubMed Web of Science ®Google Scholar
• Ly-Chatain MH: The factors affecting effectiveness of treatment in phages therapy. Front Microbiol 2014, 5:51.
   PubMed Web of Science ®Google Scholar
• Pires DP, Vilas Boas D, Sillankorva S, et al.: Phage therapy: a step forward in the treatment of Pseudomonas aeruginosa infections. J Virol 2015, 89:7449–7456.
   PubMed Web of Science ®Google Scholar
• Wright A, Hawkins CH, Anggard EE, et al.: A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clin Otolaryngol 2009, 34:349–357.
   PubMed Web of Science ®Google Scholar
• Zhao X, Chen C, Shen W, et al.: Global transcriptomic analysis of interactions between Pseudomonas aeruginosa and bacteriophage PaP3. Sci Rep 2016, 6:19237.
   PubMed Web of Science ®Google Scholar
• Hanlon GW, Denyer SP, Olliff CJ, et al.: Reduction in exopolysaccharide viscosity as an aid to bacteriophage penetration through Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 2001, 67:2746–2753.
   PubMed Web of Science ®Google Scholar
• Waters EM, Neill DR, Kaman B, et al.: Phage therapy is highly effective against chronic lung infections with Pseudomonas aeruginosa. Thorax 2017, 72:666–667.
   PubMed Web of Science ®Google Scholar
• McVay CS, Velasquez M, Fralick JA: Phage therapy of Pseudomonas aeruginosa infection in a mouse burn wound model. Antimicrob Agents Chemother 2007, 51:1934–1938.
   PubMed Web of Science ®Google Scholar
• Hawkins C, Harper D, Burch D, et al.: Topical treatment of Pseudomonas aeruginosa otitis of dogs with a bacteriophage mixture: a before/after clinical trial. Vet Microbiol 2010, 146:309–313. doi:10.1016/j.vetmic.2010.05.014
   PubMed Web of Science ®Google Scholar
• Fukuda K, Ishida W, Uchiyama J, et al.: Pseudomonas aeruginosa keratitis in mice: effects of topical bacteriophage KPP12 administration. PLoS One 2012, 7:e47742.
   PubMed Web of Science ®Google Scholar
• Fu W, Forster T, Mayer O, et al.: Bacteriophage cocktail for the prevention of biofilm formation by Pseudomonas aeruginosa on catheters in an in vitro model system. Antimicrob Agents Chemother 2010, 54:397–404.
   PubMed Web of Science ®Google Scholar
• Westwater C, Kasman LM, Schofield DA, et al.: Use of genetically engineered phage to deliver antimicrobial agents to bacteria: an alternative therapy for treatment of bacterial infections. Antimicrob Agents Chemother 2003, 47:1301–1307.
   PubMed Web of Science ®Google Scholar
• Briers Y, Walmagh M, Lavigne R: Use of bacteriophage endolysin EL188 and outer membrane permeabilizers against Pseudomonas aeruginosa. J Appl Microbiol 2011, 110:778–785.
   PubMed Web of Science ®Google Scholar
• Briers Y, Walmagh M, Van Puyenbroeck V, et al.: Engineered endolysin-based “Artilysins” to combat multidrug-resistant gram-negative pathogens. mBio 2014, 5:e01379–01314.
   PubMed Web of Science ®Google Scholar
• Lu TK, Collins JJ: Dispersing biofilms with engineered enzymatic bacteriophage. Proc Natl Acad Sci U S A 2007, 104:11197–11202.
   PubMed Web of Science ®Google Scholar
• Pei R, Lamas-Samanamud GR. Inhibition of biofilm formation by T7 bacteriophages producing quorum-quenching enzymes. Appl Environ Microbiol 2014;80(17):5340–5348.
   Web of Science ®Google Scholar
• Rossitto M, Fiscarelli EV, Rosati P: Challenges and promises for planning future clinical research into bacteriophage therapy against Pseudomonas aeruginosa in cystic fibrosis. An argumentative review. Front Microbiol 2018, 9:775.
   PubMed Web of Science ®Google Scholar
• Pabary R, Singh C, Morales S, et al.: Antipseudomonal bacteriophage reduces infective burden and inflammatory response in Murine lung. Antimicrob Agents Chemother 2016, 60:744–751.
   PubMed Web of Science ®Google Scholar
• Furfaro LL, Payne MS, Chang BJ: Bacteriophage therapy: clinical trials and regulatory hurdles. Front Cell Infect Microbiol 2018, 8:376.
   PubMed Web of Science ®Google Scholar
• Harvey H, Bondy-Denomy J, Marquis H, et al.: Pseudomonas aeruginosa defends against phages through type IV pilus glycosylation. Nat Microbiol 2018, 3:47–52.
   PubMed Web of Science ®Google Scholar
• Shen M, Zhang H, Shen W, et al.: Pseudomonas aeruginosa MutL promotes large chromosomal deletions through non-homologous end joining to prevent bacteriophage predation. Nucleic Acids Res 2018, 46:4505–4514.
   PubMed Web of Science ®Google Scholar
• Forti F, Roach DR, Cafora M, et al. Design of a broad-range bacteriophage cocktail that reduces Pseudomonas aeruginosa biofilms and treats acute infections in two animal models. Antimicrob Agents Chemother. 2018;62(6):e02573-17.
   Web of Science ®Google Scholar
• Yang Y, Shen W, Zhong Q, et al.: Development of a bacteriophage cocktail to constrain the emergence of phage-resistant Pseudomonas aeruginosa. Front Microbiol 2020, 11:327. doi:10.3389/fmicb.2020.00327
   PubMed Web of Science ®Google Scholar
• Chan BK, Turner PE, Kim S, et al.: Phage treatment of an aortic graft infected with Pseudomonas aeruginosa. Evol Med Public Health 2018, 2018:60–66. doi:10.1093/emph/eoy005
   PubMed Web of Science ®Google Scholar
• Chan BK, Sistrom M, Wertz JE, et al.: Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa. Sci Rep 2016, 6:26717.
   PubMed Web of Science ®Google Scholar
• Guo M, Feng C, Ren J, et al.: A novel antimicrobial Endolysin, LysPA26, against Pseudomonas aeruginosa. Front Microbiol 2017, 8:293.
   PubMedGoogle Scholar
• Larpin Y, Oechslin F, Moreillon P, et al.: In vitro characterization of PlyE146, a novel phage lysin that targets Gram-negative bacteria. PLoS One 2018, 13:e0192507.
   PubMed Web of Science ®Google Scholar
• Labrie SJ, Samson JE, Moineau S: Bacteriophage resistance mechanisms. Nat Rev Microbiol 2010, 8:317–327.
   PubMed Web of Science ®Google Scholar
• Hoyland-Kroghsbo NM, Paczkowski J, Mukherjee S, et al.: Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system. Proc Natl Acad Sci U S A 2017, 114:131–135.
   PubMed Web of Science ®Google Scholar
• Lin P, Pu Q, Shen G, et al.: CdpR inhibits CRISPR-cas adaptive immunity to lower anti-viral defense while avoiding self-reactivity. iScience 2019, 13:55–68.
   PubMed Web of Science ®Google Scholar
• Priebe GP, Goldberg JB: Vaccines for Pseudomonas aeruginosa: a long and winding road. Expert Rev Vaccines 2014, 13:507–519.
   PubMed Web of Science ®Google Scholar
• Doring G, Pier GB: Vaccines and immunotherapy against Pseudomonas aeruginosa. Vaccine 2008, 26:1011–1024.
   PubMed Web of Science ®Google Scholar
• Johansen HK, Gotzsche PC: Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis. Cochrane Database Syst Rev. 2015;2015(8):CD001399.
   Google Scholar
• Merakou C, Schaefers MM, Priebe GP: Progress toward the elusive Pseudomonas aeruginosa vaccine. Surg Infect (Larchmt) 2018, 19:757–768.
   PubMed Web of Science ®Google Scholar
• Doring G, Meisner C, Stern M, Flagella vaccine trial study G: a double-blind randomized placebo-controlled phase III study of a Pseudomonas aeruginosa flagella vaccine in cystic fibrosis patients. Proc Natl Acad Sci U S A 2007, 104:11020–11025.
   PubMed Web of Science ®Google Scholar
• Campodonico VL, Llosa NJ, Bentancor LV, et al.: Efficacy of a conjugate vaccine containing polymannuronic acid and flagellin against experimental Pseudomonas aeruginosa lung infection in mice. Infect Immun 2011, 79:3455–3464.
   PubMed Web of Science ®Google Scholar
• Thomsen K, Christophersen L, Jensen PO, et al.: Anti-Pseudomonas aeruginosa IgY antibodies promote bacterial opsonization and augment the phagocytic activity of polymorphonuclear neutrophils. Hum Vaccin Immunother 2016, 12:1690–1699.
   PubMed Web of Science ®Google Scholar
• Liu C, Pan X, Xia B, et al.: Construction of a protective vaccine against Lipopolysaccharide-heterologous Pseudomonas aeruginosa strains based on expression profiling of outer membrane proteins during infection. Front Immunol 2018, 9:1737.
   PubMed Web of Science ®Google Scholar
• Vincent JL: Vaccine development and passive immunization for Pseudomonas aeruginosa in critically ill patients: a clinical update. Future Microbiol 2014, 9:457–463.
   PubMed Web of Science ®Google Scholar
• Yang F, Gu J, Yang L, et al.: Protective efficacy of the trivalent Pseudomonas aeruginosa vaccine candidate PcrV-OprI-Hcp1 in Murine pneumonia and burn models. Sci Rep 2017, 7:3957. doi:10.1038/s41598-017-04029-5
   PubMed Web of Science ®Google Scholar
• Rashid MI, Naz A, Ali A, et al.: Prediction of vaccine candidates against Pseudomonas aeruginosa: an integrated genomics and proteomics approach. Genomics 2017, 109:274–283.
   PubMed Web of Science ®Google Scholar
• Bianconi I, Alcala-Franco B, Scarselli M, et al.: Genome-based approach delivers vaccine candidates against Pseudomonas aeruginosa. Front Immunol 2018, 9:3021.
   PubMed Web of Science ®Google Scholar
• Park SC, Park Y, Hahm KS: The role of antimicrobial peptides in preventing multidrug-resistant bacterial infections and biofilm formation. Int J Mol Sci 2011, 12:5971–5992.
   PubMed Web of Science ®Google Scholar
• Wen YL, Wu BJ, Kao PH, et al.: Antibacterial and membrane-damaging activities of beta-bungarotoxin B chain. J Pept Sci 2013, 19:1–8.
   PubMed Web of Science ®Google Scholar
• Chou S, Wang J, Shang L, et al.: Short, symmetric-helical peptides have narrow-spectrum activity with low resistance potential and high selectivity. Biomater Sci 2019, 7:2394–2409.
   PubMed Web of Science ®Google Scholar
• Overhage J, Campisano A, Bains M, et al.: Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun 2008, 76:4176–4182. doi:10.1128/IAI.00318-08
   PubMed Web of Science ®Google Scholar
• Dosler S, Karaaslan E: Inhibition and destruction of Pseudomonas aeruginosa biofilms by antibiotics and antimicrobial peptides. Peptides 2014, 62:32–37.
   PubMed Web of Science ®Google Scholar
• Hirt H, Gorr SU: Antimicrobial peptide GL13K is effective in reducing biofilms of Pseudomonas aeruginosa. Antimicrob Agents Chemother 2013, 57:4903–4910.
   PubMed Web of Science ®Google Scholar
• Zhu X, Shan A, Ma Z, et al.: Bactericidal efficiency and modes of action of the novel antimicrobial peptide T9W against Pseudomonas aeruginosa. Antimicrob Agents Chemother 2015, 59:3008–3017.
   PubMed Web of Science ®Google Scholar
• Papareddy P, Kasetty G, Kalle M, et al.: NLF20: an antimicrobial peptide with therapeutic potential against invasive Pseudomonas aeruginosa infection. J Antimicrob Chemother 2016, 71:170–180.
   PubMed Web of Science ®Google Scholar
• Zheng Z, Tharmalingam N, Liu Q, et al. Synergistic efficacy of Aedes aegypti antimicrobial peptide cecropin A2 and Tetracycline against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2017;61(7):e00686-17.
   Web of Science ®Google Scholar
• Casciaro B, Lin Q, Afonin S, et al.: Inhibition of Pseudomonas aeruginosa biofilm formation and expression of virulence genes by selective epimerization in the peptide Esculentin-1a(1-21)NH2. Febs J 2019, 286:3874–3891. doi:10.1111/febs.14940
   PubMed Web of Science ®Google Scholar
• Kolano L, Knappe D, Volke D, et al.: Ribosomal target-binding sites of antimicrobial peptides Api137 and Onc112 are conserved among pathogens providing new lead structures to develop novel broad-spectrum antibiotics. Chembiochem 2020. doi:10.1002/cbic.202000109
   PubMed Web of Science ®Google Scholar
• Chou S, Li Q, Nina Z, et al.: Peptides with triplet-Tryptophan-pivot promoted pathogenic bacteria membrane defects. Front Microbiol 2020, 11:537. doi:10.3389/fmicb.2020.00537
   PubMed Web of Science ®Google Scholar
• Giacometti A, Cirioni O, Barchiesi F, et al.: In-vitro activity of cationic peptides alone and in combination with clinically used antimicrobial agents against Pseudomonas aeruginosa. J Antimicrob Chemother 1999, 44:641–645.
   PubMed Web of Science ®Google Scholar
• Carneiro VA, de Oliveira ST, Silva RL, et al.: Antimicrobial and antibiofilm activity of Lys-[Trp6]hy-a1 combined with Ciprofloxacin against Gram-negative bacteria. Protein Pept Lett 2020. 27 doi:10.2174/0929866527666200416145549
   PubMed Web of Science ®Google Scholar
• Ferrer-Espada R, Sanchez-Gomez S, Pitts B, et al.: Permeability enhancers sensitize β-lactamase-expressing Enterobacteriaceae and Pseudomonas aeruginosa to β-lactamase inhibitors, thereby restoring their β-lactam susceptibility. Int J Antimicrob Agents 2020;56:105986.
   PubMed Web of Science ®Google Scholar
• Aoki W, Ueda M: Characterization of antimicrobial peptides toward the development of novel antibiotics. Pharmaceuticals (Basel) 2013, 6:1055–1081.
   PubMedGoogle Scholar
• Maisuria VB, Los Santos YL, Tufenkji N, et al.: Cranberry-derived proanthocyanidins impair virulence and inhibit quorum sensing of Pseudomonas aeruginosa. Sci Rep 2016, 6:30169. doi:10.1038/srep30169
   PubMed Web of Science ®Google Scholar
• Chang CY, Krishnan T, Wang H, et al.: Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target. Sci Rep 2014, 4:7245.
   PubMed Web of Science ®Google Scholar
• Karaiskos I, Souli M, Giamarellou H: Plazomicin: an investigational therapy for the treatment of urinary tract infections. Expert Opin Investig Drugs 2015, 24:1501–1511. doi:10.1517/13543784.2015.1095180
   PubMed Web of Science ®Google Scholar
• Stefani S, Campana S, Cariani L, et al.: Relevance of multidrug-resistant Pseudomonas aeruginosa infections in cystic fibrosis. Int J Med Microbiol 2017, 307:353–362.
   PubMed Web of Science ®Google Scholar
• Ruiz-Garbajosa P, Canton R: Epidemiology of antibiotic resistance in Pseudomonas aeruginosa. Implications for empiric and definitive therapy. Rev Esp Quimioter 2017, 30 Suppl 1:8–12.
   PubMedGoogle Scholar
• Subedi D, Vijay AK, Willcox M: Overview of mechanisms of antibiotic resistance in Pseudomonas aeruginosa: an ocular perspective. Clin Exp Optom 2018, 101:162–171.
   PubMed Web of Science ®Google Scholar
• Jeukens J, Freschi L, Kukavica-Ibrulj I, et al.: Genomics of antibiotic-resistance prediction in Pseudomonas aeruginosa. Ann N Y Acad Sci 2019, 1435:5–17. doi:10.1111/nyas.13358
   PubMed Web of Science ®Google Scholar
• Pang Z, Raudonis R, Glick BR, et al.: Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnol Adv 2019, 37:177–192. doi:10.1016/j.biotechadv.2018.11.013
   PubMed Web of Science ®Google Scholar
• Folkesson A, Jelsbak L, Yang L, et al.: Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective. Nat Rev Microbiol 2012, 10:841–851. doi:10.1038/nrmicro2907
   PubMed Web of Science ®Google Scholar
• Yang L, Jelsbak L, Marvig RL, et al.: Evolutionary dynamics of bacteria in a human host environment. Proc Natl Acad Sci U S A 2011, 108:7481–7486.
   PubMed Web of Science ®Google Scholar
• Hoffman LR, Kulasekara HD, Emerson J, et al.: Pseudomonas aeruginosa lasR mutants are associated with cystic fibrosis lung disease progression. J Cyst Fibros 2009, 8:66–70.
   PubMed Web of Science ®Google Scholar
• Valentini M, Gonzalez D, Mavridou DA, et al.: Lifestyle transitions and adaptive pathogenesis of Pseudomonas aeruginosa. Curr Opin Microbiol 2018, 41:15–20.
   PubMed Web of Science ®Google Scholar
• Furukawa S, Kuchma SL, O’Toole GA: Keeping their options open: acute versus persistent infections. J Bacteriol 2006, 188:1211–1217.
   PubMed Web of Science ®Google Scholar
• Goodman AL, Kulasekara B, Rietsch A, et al.: A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa. Dev Cell 2004, 7:745–754. doi:10.1016/j.devcel.2004.08.020
   PubMed Web of Science ®Google Scholar
• Goodman AL, Merighi M, Hyodo M, et al.: Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen. Genes Dev 2009, 23:249–259.
   PubMed Web of Science ®Google Scholar
• Ventre I, Goodman AL, Vallet-Gely I, et al.: Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes. Proc Natl Acad Sci U S A 2006, 103:171–176.
   PubMed Web of Science ®Google Scholar
• Kay E, Humair B, Denervaud V, et al.: Two GacA-dependent small RNAs modulate the quorum-sensing response in Pseudomonas aeruginosa. J Bacteriol 2006, 188:6026–6033. doi:10.1128/JB.00409-06
   PubMed Web of Science ®Google Scholar
• Brencic A, Lory S: Determination of the regulon and identification of novel mRNA targets of Pseudomonas aeruginosa RsmA. Mol Microbiol 2009, 72:612–632.
   PubMed Web of Science ®Google Scholar
• Frangipani E, Visaggio D, Heeb S, et al.: The Gac/Rsm and cyclic-di-GMP signalling networks coordinately regulate iron uptake in Pseudomonas aeruginosa. Environ Microbiol 2014, 16:676–688.
   PubMed Web of Science ®Google Scholar
• Broder UN, Jaeger T, Jenal U: LadS is a calcium-responsive kinase that induces acute-to-chronic virulence switch in Pseudomonas aeruginosa. Nat Microbiol 2016, 2:16184.
   PubMed Web of Science ®Google Scholar
• Damron FH, Qiu D, Yu HD: The Pseudomonas aeruginosa sensor kinase KinB negatively controls alginate production through AlgW-dependent MucA proteolysis. J Bacteriol 2009, 191:2285–2295.
   PubMed Web of Science ®Google Scholar
• Chand NS, Clatworthy AE, Hung DT: The two-component sensor KinB acts as a phosphatase to regulate Pseudomonas aeruginosa Virulence. J Bacteriol 2012, 194:6537–6547.
   PubMedGoogle Scholar
• Intile PJ, Diaz MR, Urbanowski ML, et al.: The AlgZR two-component system recalibrates the RsmAYZ posttranscriptional regulatory system to inhibit expression of the Pseudomonas aeruginosa type III secretion system. J Bacteriol 2014, 196:357–366.
   PubMed Web of Science ®Google Scholar
• Deretic V, Konyecsni WM: A procaryotic regulatory factor with a histone H1-like carboxy-terminal domain: clonal variation of repeats within algP, a gene involved in regulation of mucoidy in Pseudomonas aeruginosa. J Bacteriol 1990, 172:5544–5554.
   PubMed Web of Science ®Google Scholar
• Balasubramanian D, Schneper L, Merighi M, et al.: The regulatory repertoire of Pseudomonas aeruginosa AmpC ss-lactamase regulator AmpR includes virulence genes. PLoS One 2012, 7:e34067.
   PubMed Web of Science ®Google Scholar
• Jones CJ, Newsom D, Kelly B, et al.: ChIP-Seq and RNA-Seq reveal an AmrZ-mediated mechanism for cyclic di-GMP synthesis and biofilm development by Pseudomonas aeruginosa. PLoS Pathog 2014, 10:e1003984.
   PubMed Web of Science ®Google Scholar
• Baynham PJ, Ramsey DM, Gvozdyev BV, et al.: The Pseudomonas aeruginosa ribbon-helix-helix DNA-binding protein AlgZ (AmrZ) controls twitching motility and biogenesis of type IV pili. J Bacteriol 2006, 188:132–140.
   PubMedGoogle Scholar
• Allsopp LP, Wood TE, Howard SA, et al.: RsmA and AmrZ orchestrate the assembly of all three type VI secretion systems in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 2017, 114:7707–7712.
   PubMed Web of Science ®Google Scholar
• Oglesby AG, Farrow JM 3rd, Lee JH, et al.: The influence of iron on Pseudomonas aeruginosa physiology: a regulatory link between iron and quorum sensing. J Biol Chem 2008, 283:15558–15567. doi:10.1074/jbc.M707840200
   PubMed Web of Science ®Google Scholar
• Rompf A, Hungerer C, Hoffmann T, et al.: Regulation of Pseudomonas aeruginosa hemF and hemN by the dual action of the redox response regulators Anr and Dnr. Mol Microbiol 1998, 29:985–997.
   PubMed Web of Science ®Google Scholar
• Ye RW, Haas D, Ka JO, et al.: Anaerobic activation of the entire denitrification pathway in Pseudomonas aeruginosa requires Anr, an analog of Fnr. J Bacteriol 1995, 177:3606–3609.
   PubMed Web of Science ®Google Scholar
• Hammond JH, Dolben EF, Smith TJ, et al.: Links between Anr and Quorum Sensing in Pseudomonas aeruginosa Biofilms. J Bacteriol 2015, 197:2810–2820.
   PubMed Web of Science ®Google Scholar
• Park SM, Lu CD, Abdelal AT: Purification and characterization of an arginine regulatory protein, ArgR, from Pseudomonas aeruginosa and its interactions with the control regions for the car, argF, and aru operons. J Bacteriol 1997, 179:5309–5317. doi:10.1128/JB.179.17.5309-5317.1997
   PubMed Web of Science ®Google Scholar
• Petrova OE, Sauer K: The novel two-component regulatory system BfiSR regulates biofilm development by controlling the small RNA rsmZ through CafA. J Bacteriol 2010, 192:5275–5288.
   PubMed Web of Science ®Google Scholar
• Petrova OE, Sauer K, A novel signaling network essential for regulating Pseudomonas aeruginosa biofilm development. PLoS Pathog 2009;5(11):e1000668.
   Web of Science ®Google Scholar
• Petrova OE, Schurr JR, Schurr MJ, et al.: The novel Pseudomonas aeruginosa two-component regulator BfmR controls bacteriophage-mediated lysis and DNA release during biofilm development through PhdA. Mol Microbiol 2011, 81:767–783. doi:10.1111/j.1365-2958.2011.07733.x
   PubMed Web of Science ®Google Scholar
• Cao Q, Wang Y, Chen F, et al.: A novel signal transduction pathway that modulates rhl quorum sensing and bacterial virulence in Pseudomonas aeruginosa. PLoS Pathog 2014, 10:e1004340.
   PubMed Web of Science ®Google Scholar
• Yeung AT, Bains M, Hancock RE: The sensor kinase CbrA is a global regulator that modulates metabolism, virulence, and antibiotic resistance in Pseudomonas aeruginosa. J Bacteriol 2011, 193:918–931. doi:10.1128/JB.00911-10
   PubMed Web of Science ®Google Scholar
• Caille O, Rossier C, Perron K: A copper-activated two-component system interacts with zinc and imipenem resistance in Pseudomonas aeruginosa. J Bacteriol 2007, 189:4561–4568. doi:10.1128/JB.00095-07
   PubMed Web of Science ®Google Scholar
• Teitzel GM, Geddie A, De Long SK, et al.: Survival and growth in the presence of elevated copper: transcriptional profiling of copper-stressed Pseudomonas aeruginosa. J Bacteriol 2006, 188:7242–7256.
   PubMed Web of Science ®Google Scholar
• Dieppois G, Ducret V, Caille O, et al.: The transcriptional regulator CzcR modulates antibiotic resistance and quorum sensing in Pseudomonas aeruginosa. PLoS One 2012, 7:e38148.
   PubMed Web of Science ®Google Scholar
• Lundgren BR, Bailey FJ, Moley G, et al.: DdaR (PA1196) regulates expression of dimethylarginine dimethylaminohydrolase for the metabolism of methylarginines in Pseudomonas aeruginosa PAO1. J Bacteriol. J Bacteriol. 2017;199(8):e00001-17.
   Web of Science ®Google Scholar
• Branny P, Pearson JP, Pesci EC, et al.: Inhibition of quorum sensing by a Pseudomonas aeruginosa dksA homologue. J Bacteriol 2001, 183:1531–1539.
   PubMed Web of Science ®Google Scholar
• Frank DW: The exoenzyme S regulon of Pseudomonas aeruginosa. Mol Microbiol 1997, 26:621–629.
   PubMed Web of Science ®Google Scholar
• Arora SK, Ritchings BW, Almira EC, et al.: A transcriptional activator, FleQ, regulates mucin adhesion and flagellar gene expression in Pseudomonas aeruginosa in a cascade manner. J Bacteriol 1997, 179:5574–5581. doi:10.1128/JB.179.17.5574-5581.1997
   PubMed Web of Science ®Google Scholar
• Baraquet C, Harwood CS: Cyclic diguanosine monophosphate represses bacterial flagella synthesis by interacting with the Walker A motif of the enhancer-binding protein FleQ. Proc Natl Acad Sci U S A 2013, 110:18478–18483.
   PubMed Web of Science ®Google Scholar
• Hickman JW, Harwood CS: Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor. Mol Microbiol 2008, 69:376–389.
   PubMed Web of Science ®Google Scholar
• Jyot J, Dasgupta N, Ramphal R: FleQ, the major flagellar gene regulator in Pseudomonas aeruginosa, binds to enhancer sites located either upstream or atypically downstream of the RpoN binding site. J Bacteriol 2002, 184:5251–5260.
   PubMed Web of Science ®Google Scholar
• Hassett DJ, Sokol PA, Howell ML, et al.: Ferric uptake regulator (Fur) mutants of Pseudomonas aeruginosa demonstrate defective siderophore-mediated iron uptake, altered aerobic growth, and decreased superoxide dismutase and catalase activities. J Bacteriol 1996, 178:3996–4003. doi:10.1128/JB.178.14.3996-4003.1996
   PubMed Web of Science ®Google Scholar
• Hassett DJ, Howell ML, Ochsner UA, et al.: An operon containing fumC and sodA encoding fumarase C and manganese superoxide dismutase is controlled by the ferric uptake regulator in Pseudomonas aeruginosa: fur mutants produce elevated alginate levels. J Bacteriol 1997, 179:1452–1459.
   PubMed Web of Science ®Google Scholar
• Ochsner UA, Vasil AI, Vasil ML: Role of the ferric uptake regulator of Pseudomonas aeruginosa in the regulation of siderophores and exotoxin A expression: purification and activity on iron-regulated promoters. J Bacteriol 1995, 177:7194–7201. doi:10.1128/JB.177.24.7194-7201.1995
   PubMed Web of Science ®Google Scholar
• Brencic A, McFarland KA, McManus HR, et al.: The GacS/GacA signal transduction system of Pseudomonas aeruginosa acts exclusively through its control over the transcription of the RsmY and RsmZ regulatory small RNAs. Mol Microbiol 2009, 73:434–445.
   PubMed Web of Science ®Google Scholar
• Wargo MJ, Szwergold BS, Hogan DA: Identification of two gene clusters and a transcriptional regulator required for Pseudomonas aeruginosa glycine betaine catabolism. J Bacteriol 2008, 190:2690–2699.
   PubMedGoogle Scholar
• Blus-Kadosh I, Zilka A, Yerushalmi G, et al.: The effect of pstS and phoB on quorum sensing and swarming motility in Pseudomonas aeruginosa. PLoS One 2013, 8:e74444. doi:10.1371/journal.pone.0074444
   PubMedGoogle Scholar
• Faure LM, Llamas MA, Bastiaansen KC, et al.: Phosphate starvation relayed by PhoB activates the expression of the Pseudomonas aeruginosa sigmavreI ECF factor and its target genes. Microbiology 2013, 159:1315–1327.
   PubMed Web of Science ®Google Scholar
• Monds RD, Silby MW, Mahanty HK: Expression of the Pho regulon negatively regulates biofilm formation by Pseudomonas aureofaciens PA147-2. Mol Microbiol 2001, 42:415–426. doi:10.1046/j.1365-2958.2001.02641.x
   PubMed Web of Science ®Google Scholar
• Gooderham WJ, Gellatly SL, Sanschagrin F, et al.: The sensor kinase PhoQ mediates virulence in Pseudomonas aeruginosa. Microbiology 2009, 155:699–711.
   PubMed Web of Science ®Google Scholar
• Ernst RK, Yi EC, Guo L, et al.: Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science 1999, 286:1561–1565.
   PubMed Web of Science ®Google Scholar
• Macfarlane EL, Kwasnicka A, Ochs MM, et al.: PhoP-PhoQ homologues in Pseudomonas aeruginosa regulate expression of the outer-membrane protein OprH and polymyxin B resistance. Mol Microbiol 1999, 34:305–316.
   PubMed Web of Science ®Google Scholar
• Ramsey MM, Whiteley M: Pseudomonas aeruginosa attachment and biofilm development in dynamic environments. Mol Microbiol 2004, 53:1075–1087. doi:10.1111/j.1365-2958.2004.04181.x
   PubMed Web of Science ®Google Scholar
• McPhee JB, Bains M, Winsor G, et al.: Contribution of the PhoP-PhoQ and PmrA-PmrB two-component regulatory systems to Mg2+-induced gene regulation in Pseudomonas aeruginosa. J Bacteriol 2006, 188:3995–4006.
   PubMed Web of Science ®Google Scholar
• Gilbert KB, Kim TH, Gupta R, et al.: Global position analysis of the Pseudomonas aeruginosa quorum-sensing transcription factor LasR. Mol Microbiol 2009, 73:1072–1085.
   PubMed Web of Science ®Google Scholar
• Wade DS, Calfee MW, Rocha ER, et al.: Regulation of Pseudomonas quinolone signal synthesis in Pseudomonas aeruginosa. J Bacteriol 2005, 187:4372–4380. doi:10.1128/JB.187.13.4372-4380.2005
   PubMed Web of Science ®Google Scholar
• Ueda A, Wood TK. Connecting quorum sensing, c-di-GMP, pel polysaccharide, and biofilm formation in Pseudomonas aeruginosa through tyrosine phosphatase TpbA (PA3885). PLoS Pathog 2009;5(6):e1000483.
   Web of Science ®Google Scholar
• Tian ZX, Fargier E, Mac Aogain M, et al.: Transcriptome profiling defines a novel regulon modulated by the LysR-type transcriptional regulator MexT in Pseudomonas aeruginosa. Nucleic Acids Res 2009, 37:7546–7559.
   PubMed Web of Science ®Google Scholar
• Vallet I, Diggle SP, Stacey RE, et al.: Biofilm formation in Pseudomonas aeruginosa: fimbrial cup gene clusters are controlled by the transcriptional regulator MvaT. J Bacteriol 2004, 186:2880–2890. doi:10.1128/JB.186.9.2880-2890.2004
   PubMedGoogle Scholar
• Maura D, Hazan R, Kitao T, et al.: Evidence for direct control of virulence and defense gene circuits by the Pseudomonas aeruginosa Quorum sensing regulator, MvfR. Sci Rep 2016, 6:34083.
   PubMed Web of Science ®Google Scholar
• Stickland HG, Davenport PW, Lilley KS, et al.: Mutation of nfxB causes global changes in the physiology and metabolism of Pseudomonas aeruginosa. J Proteome Res 2010, 9:2957–2967. doi:10.1021/pr9011415
   PubMed Web of Science ®Google Scholar
• Purssell A, Poole K: Functional characterization of the NfxB repressor of the mexCD-oprJ multidrug efflux operon of Pseudomonas aeruginosa. Microbiology 2013, 159:2058–2073.
   PubMed Web of Science ®Google Scholar
• Wang D, Seeve C, Pierson LS 3rd, et al.: Transcriptome profiling reveals links between ParS/ParR, MexEF-OprN, and quorum sensing in the regulation of adaptation and virulence in Pseudomonas aeruginosa. BMC Genomics 2013, 14:618.
   PubMed Web of Science ®Google Scholar
• Michel L, Gonzalez N, Jagdeep S, et al.: PchR-box recognition by the AraC-type regulator PchR of Pseudomonas aeruginosa requires the siderophore pyochelin as an effector. Mol Microbiol 2005, 58:495–509.
   PubMed Web of Science ®Google Scholar
• Heinrichs DE, Poole K: PchR, a regulator of ferripyochelin receptor gene (fptA) expression in Pseudomonas aeruginosa, functions both as an activator and as a repressor. J Bacteriol 1996, 178:2586–2592.
   PubMed Web of Science ®Google Scholar
• Kilmury SLN, Burrows LL: The Pseudomonas aeruginosa PilSR two-component system regulates both twitching and swimming motilities. MBio. 2018;9(4):e01310-18.
   Google Scholar
• Liang H, Li L, Dong Z, et al.: The YebC family protein PA0964 negatively regulates the Pseudomonas aeruginosa quinolone signal system and pyocyanin production. J Bacteriol 2008, 190:6217–6227. doi:10.1128/JB.00428-08
   PubMed Web of Science ®Google Scholar
• McPhee JB, Lewenza S, Hancock RE: Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. Mol Microbiol 2003, 50:205–217.
   PubMed Web of Science ®Google Scholar
• Moskowitz SM, Ernst RK, Miller SI: PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A. J Bacteriol 2004, 186:575–579.
   PubMed Web of Science ®Google Scholar
• Matsui H, Sano Y, Ishihara H, et al.: Regulation of pyocin genes in Pseudomonas aeruginosa by positive (prtN) and negative (prtR) regulatory genes. J Bacteriol 1993, 175:1257–1263.
   PubMed Web of Science ®Google Scholar
• Carty NL, Layland N, Colmer-Hamood JA, et al.: PtxR modulates the expression of QS-controlled virulence factors in the Pseudomonas aeruginosa strain PAO1. Mol Microbiol 2006, 61:782–794.
   PubMed Web of Science ®Google Scholar
• Daddaoua A, Fillet S, Fernandez M, et al.: Genes for carbon metabolism and the ToxA virulence factor in Pseudomonas aeruginosa are regulated through molecular interactions of PtxR and PtxS. PLoS One 2012, 7:e39390. doi:10.1371/journal.pone.0039390
   PubMed Web of Science ®Google Scholar
• Ledgham F, Ventre I, Soscia C, et al.: Interactions of the quorum sensing regulator QscR: interaction with itself and the other regulators of Pseudomonas aeruginosa LasR and RhlR. Mol Microbiol 2003, 48:199–210.
   PubMed Web of Science ®Google Scholar
• Mukherjee S, Moustafa D, Smith CD, et al.: The RhlR quorum-sensing receptor controls Pseudomonas aeruginosa pathogenesis and biofilm development independently of its canonical homoserine lactone autoinducer. PLoS Pathog 2017, 13:e1006504.
   PubMed Web of Science ®Google Scholar
• Nicastro GG, Boechat AL, Abe CM, et al.: Pseudomonas aeruginosa PA14 cupD transcription is activated by the RcsB response regulator, but repressed by its putative cognate sensor RcsC. FEMS Microbiol Lett 2009, 301:115–123.
   PubMed Web of Science ®Google Scholar
• Mikkelsen H, Ball G, Giraud C, et al.: Expression of Pseudomonas aeruginosa CupD fimbrial genes is antagonistically controlled by RcsB and the EAL-containing PvrR response regulators. PLoS One 2009, 4:e6018.
   PubMed Web of Science ®Google Scholar
• Kulasekara HD, Ventre I, Kulasekara BR, et al.: A novel two-component system controls the expression of Pseudomonas aeruginosa fimbrial cup genes. Mol Microbiol 2005, 55:368–380. doi:10.1111/j.1365-2958.2004.04402.x
   PubMed Web of Science ®Google Scholar
• Suh SJ, Silo-Suh L, Woods DE, et al.: Effect of rpoS mutation on the stress response and expression of virulence factors in Pseudomonas aeruginosa. J Bacteriol 1999, 181:3890–3897.
   PubMed Web of Science ®Google Scholar
• Irie Y, Starkey M, Edwards AN, et al.: Pseudomonas aeruginosa biofilm matrix polysaccharide Psl is regulated transcriptionally by RpoS and post-transcriptionally by RsmA. Mol Microbiol 2010, 78:158–172.
   PubMed Web of Science ®Google Scholar
• Kang H, Gan J, Zhao J, et al.: Crystal structure of Pseudomonas aeruginosa RsaL bound to promoter DNA reaffirms its role as a global regulator involved in quorum-sensing. Nucleic Acids Res 2017, 45:699–710. doi:10.1093/nar/gkw954
   PubMed Web of Science ®Google Scholar
• Lundgren BR, Sarwar Z, Feldman KS, et al. SfnR2 Regulates Dimethyl Sulfide-Related Utilization in Pseudomonas aeruginosa PAO1. J Bacteriol. 2019;201(4):e00606-18.
   Web of Science ®Google Scholar
• Palma M, Zurita J, Ferreras JA, et al.: Pseudomonas aeruginosa SoxR does not conform to the archetypal paradigm for SoxR-dependent regulation of the bacterial oxidative stress adaptive response. Infect Immun 2005, 73:2958–2966.
   PubMed Web of Science ®Google Scholar
• LaBauve AE, Wargo MJ. Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung. PLoS Pathog 2014;10(1):e1003889.
   Web of Science ®Google Scholar
• Wozniak DJ, Cram DC, Daniels CJ, et al.: Nucleotide sequence and characterization of toxR: a gene involved in exotoxin A regulation in Pseudomonas aeruginosa. Nucleic Acids Res 1987, 15:2123–2135.
   PubMed Web of Science ®Google Scholar
• Albus AM, Pesci EC, Runyen-Janecky LJ, et al.: Vfr controls quorum sensing in Pseudomonas aeruginosa. J Bacteriol 1997, 179:3928–3935.
   PubMed Web of Science ®Google Scholar
• Smith RS, Wolfgang MC, Lory S: An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia. Infect Immun 2004, 72:1677–1684.
   PubMed Web of Science ®Google Scholar
• Boucher RC: New concepts of the pathogenesis of cystic fibrosis lung disease. Eur Respir J 2004, 23:146–158.
   PubMed Web of Science ®Google Scholar
• Geller DE: Aerosol antibiotics in cystic fibrosis. Respir Care 2009, 54:658–670.
   PubMed Web of Science ®Google Scholar
• Rosenfeld M, Ramsey BW, Gibson RL: Pseudomonas acquisition in young patients with cystic fibrosis: pathophysiology, diagnosis, and management. Curr Opin Pulm Med 2003, 9:492–497.
   PubMed Web of Science ®Google Scholar
• Gaspar MC, Couet W, Olivier JC, et al.: Pseudomonas aeruginosa infection in cystic fibrosis lung disease and new perspectives of treatment: a review. Eur J Clin Microbiol Infect Dis 2013, 32:1231–1252.
   PubMed Web of Science ®Google Scholar
• Diard M, Hardt WD: Evolution of bacterial virulence. FEMS Microbiol Rev 2017, 41:679–697. doi:10.1093/femsre/fux023
   PubMed Web of Science ®Google Scholar
• Casadevall A, Pirofski LA. Host-pathogen interactions: redefining the basic concepts of virulence and pathogenicity. Infect Immun. 1999;67(8):3703–3713. doi:10.1128/IAI.67.8.3703-3713.1999
   Web of Science ®Google Scholar
• Thiele I, Palsson BO: A protocol for generating a high-quality genome-scale metabolic reconstruction. Nat Protoc 2010, 5:93–121.
   PubMed Web of Science ®Google Scholar
• Chavali AK, D’Auria KM, Hewlett EL, et al.: A metabolic network approach for the identification and prioritization of antimicrobial drug targets. Trends Microbiol 2012, 20:113–123.
   PubMed Web of Science ®Google Scholar
• Bartell JA, Blazier AS, Yen P, et al.: Reconstruction of the metabolic network of Pseudomonas aeruginosa to interrogate virulence factor synthesis. Nat Commun 2017, 8:14631.
   PubMed Web of Science ®Google Scholar
• Panayidou S, Georgiades K, Christofi T, et al.: Pseudomonas aeruginosa core metabolism exerts a widespread growth-independent control on virulence. Sci Rep 2020, 10:9505.
   PubMed Web of Science ®Google Scholar