1,253
Views
0
CrossRef citations to date
0
Altmetric
Research Paper

Targeting virulence regulation to disarm Acinetobacter baumannii pathogenesis

ORCID Icon, , , , , , , , , , , , , , , , , & ORCID Icon show all
Pages 1868-1883 | Received 30 Jun 2022, Accepted 09 Oct 2022, Published online: 19 Oct 2022

References

  • Boucher HW, Talbot GH, Bradley JS, et al. Bad bugs, no drugs: no ESKAPE! An update from the infectious diseases society of America. Clin Infect Dis off Publ Infect Dis Soc Am. 2009;48(1):1–12. DOI:10.1086/595011
  • Cassini A, Högberg LD, Plachouras D, et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European economic area in 2015: a population-level modelling analysis. Lancet Infect Dis. 2019;19(1):56–66. DOI:10.1016/S1473-3099(18)30605-4
  • Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318–327. DOI:10.1016/S1473-3099(17)30753-3
  • Lötsch F, Albiger B, Monnet DL, et al. Epidemiological situation, laboratory capacity and preparedness for carbapenem-resistant acinetobacter baumannii in Europe, 2019. Eurosurveillance. 2020;25(45):2001735. DOI:10.2807/1560-7917.ES.2020.25.45.2001735
  • Hu F, Zhu D, Wang F, et al. Current status and trends of antibacterial resistance in China. Clin Infect Dis off Publ Infect Dis Soc Am. 2018;67(suppl_2):S128–134 doi:10.1093/cid/ciy657.
  • Jernigan JA, Hatfield KM, Wolford H, et al. Multidrug-resistant bacterial infections in U.S. hospitalized patients, 2012–2017. N Engl J Med. 2020;382(14):1309–1319. DOI:10.1056/NEJMoa1914433
  • Cox G, Sieron A, King AM, et al. A common platform for antibiotic dereplication and adjuvant discovery. Cell Chem Biol. 2017;24(1):98–109. DOI:10.1016/j.chembiol.2016.11.011
  • Allen RC, Popat R, Diggle SP, et al. Targeting virulence: can we make evolution-proof drugs? Nat Rev Microbiol. 2014;12(4):300–308 doi:10.1038/nrmicro3232.
  • Clatworthy AE, Pierson E, Hung DT. Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol. 2007;3(9):541–548 doi:10.1038/nchembio.2007.24.
  • Morris FC, Dexter C, Kostoulias X, et al. The mechanisms of disease caused by Acinetobacter baumannii. Front Microbiol. 2019;10:10 doi:10.3389/fmicb.2019.01601.
  • Geisinger E, Huo W, Hernandez-Bird J, et al. Acinetobacter baumannii: envelope determinants that control drug resistance, virulence, and surface variability. Annu Rev Microbiol. 2019;73(1):481–506 doi:10.1146/annurev-micro-020518-115714.
  • De Silva PM, Kumar A. Signal transduction proteins in Acinetobacter baumannii: role in antibiotic resistance, virulence, and potential as drug targets. Front Microbiol. 2019;10:49 doi:10.3389/fmicb.2019.00049.
  • Beier D, Gross R. Regulation of bacterial virulence by two-component systems. Curr Opin Microbiol. 2006;9(2):143–152 doi:10.1016/j.mib.2006.01.005.
  • Tiwari S, Jamal SB, Hassan SS, et al. Two-component signal transduction systems of pathogenic bacteria as targets for antimicrobial therapy: an overview. Front Microbiol. 2017;8:1878 doi:10.3389/fmicb.2017.01878.
  • Yoshida T, Qin L, Egger LA, et al. Transcription regulation of ompF and ompC by a single transcription factor, OmpR. J Biol Chem. 2006;281(25):17114–17123 doi:10.1074/jbc.M602112200.
  • Barbieri CM, Wu T, Stock AM. Comprehensive analysis of OmpR phosphorylation, dimerization, and DNA binding supports a canonical model for activation. J Mol Biol. 2013;425(10):1612–1626 doi:10.1016/j.jmb.2013.02.003.
  • Kenney LJ, Anand GS. EnvZ/OmpR two-component signaling: an archetype system that can function non-canonically. EcoSal Plus. 2020;9(1):9 doi:10.1128/ecosalplus.ESP-0001-2019.
  • Seo SW, Gao Y, Kim D, et al. Revealing genome-scale transcriptional regulatory landscape of OmpR highlights its expanded regulatory roles under osmotic stress in Escherichia coli K-12 MG1655. Sci Rep. 2017;7(1):2181. DOI:10.1038/s41598-017-02110-7
  • Shimada T, Takada H, Yamamoto K, et al. Expanded roles of two-component response regulator OmpR in Escherichia coli: genomic SELEX search for novel regulation targets. Genes Cells. 2015;20(11):915–931 doi:10.1111/gtc.12282.
  • Tipton KA, Rather PN. An ompR-envZ two-component system ortholog regulates phase variation, osmotic tolerance, motility, and virulence in Acinetobacter baumannii strain AB5075. J Bacteriol. 2017;199(3):e00705–16 doi:10.1128/JB.00705-16.
  • Bruhn KW, Pantapalangkoor P, Nielsen T, et al. Host fate is rapidly determined by innate effector-microbial interactions during Acinetobacter baumannii bacteremia. J Infect Dis. 2015;211:1296–1305 doi:10.1093/infdis/jiu593.
  • Champion OL, Cooper IAM, James SL, et al. Galleria mellonella as an alternative infection model for yersinia pseudotuberculosis. Microbiology. 2009;155(5):1516–1522. DOI:10.1099/mic.0.026823-0
  • Ramarao N, Nielsen-Leroux C, Lereclus D. The insect galleria mellonella as a powerful infection model to investigate bacterial pathogenesis. J Vis Exp JoVe. 2012;4392(70). DOI:10.3791/4392
  • Rhee JE, Sheng W, Morgan LK, et al. Amino acids important for DNA recognition by the response regulator OmpR. J Biol Chem. 2008;283(13):8664–8677 doi:10.1074/jbc.M705550200.
  • Kato N, Tsuzuki M, Aiba H, et al. Gene activation by theEscherichia coli positive regulator OmpR: a mutational study of the DNA-binding domain of OmpR. Mol Gen Genet MGG. 1995;248(4):399–406 doi:10.1007/BF02191639.
  • Gebhardt MJ, Gallagher LA, Jacobson RK, et al. Joint transcriptional control of virulence and resistance to antibiotic and environmental stress in Acinetobacter baumannii. MBio. 2015;6:e01660–15. DOI:10.1128/mBio.01660-15
  • Blériot C, Effantin G, Lagarde F, et al. RcnB is a periplasmic protein essential for maintaining intracellular Ni and Co concentrations in Escherichia coli. J Bacteriol. 2011;193(15):3785–3793 doi:10.1128/JB.05032-11.
  • Bergstrom LC, Qin L, Harlocker SL, et al. Hierarchical and co-operative binding of OmpR to a fusion construct containing the ompC and ompF upstream regulatory sequences of Escherichia coli. Genes Cells. 1998;3(12):777–788 doi:10.1046/j.1365-2443.1998.00228.x.
  • Head CG, Tardy A, Kenney LJ. Relative binding affinities of OmpR and OmpR-phosphate at the ompF and ompC regulatory sites. J Mol Biol. 1998;281(5):857–870 doi:10.1006/jmbi.1998.1985.
  • Bailey TL, Boden M, Buske FA, et al. MEME suite: tools for motif discovery and searching. Nucleic Acids Res. 2009;37(Web Server):W202–208. DOI:10.1093/nar/gkp335
  • Martínez-Hackert E, Stock AM. The DNA-binding domain of OmpR: crystal structures of a winged helix transcription factor. Structure. 1997;5(1):109–124 doi:10.1016/S0969-2126(97)00170-6.
  • Sadotra S, Lou Y-C, Tang H-C, et al. Structural basis for promoter DNA recognition by the response regulator OmpR. J Struct Biol. 2021;213(1):107638 doi:10.1016/j.jsb.2020.107638.
  • Geppert T, Hoy B, Wessler S, et al. Context-based identification of protein-protein interfaces and “hot-spot” residues. Chem Biol. 2011;18(3):344–353 doi:10.1016/j.chembiol.2011.01.005.
  • Wolber G, Langer TL. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J Chem Inf Model. 2005;45(1):160–169 doi:10.1021/ci049885e.
  • Chien Y, Manna AC, Projan SJ, et al. SarA, a global regulator of virulence determinants instaphylococcus aureus, binds to a conserved motif essential for sar-dependent gene regulation. J Biol Chem. 1999;274(52):37169–37176 doi:10.1074/jbc.274.52.37169.
  • Colclough AL, Alav I, Whittle EE, et al. RND efflux pumps in gram-negative bacteria; regulation, structure and role in antibiotic resistance. Future Microbiol. 2020;15(2):143–157. DOI:10.2217/fmb-2019-0235
  • Pérez-Varela M, Corral J, Aranda J, et al. Roles of efflux pumps from different superfamilies in the surface-associated motility and virulence of Acinetobacter baumannii ATCC 17978. Antimicrob Agents Chemother. 2019;63(3):63 doi:10.1128/AAC.02190-18.
  • Richmond GE, Evans LP, Anderson MJ, et al. the acinetobacter baumannii two-component system AdeRS regulates genes required for multidrug efflux, biofilm formation, and virulence in a strain-specific manner. MBio. 2016;7(3). DOI:10.1128/mBio.00430-16
  • Yoon E-J, Chabane YN, Goussard S, et al. Contribution of resistance-nodulation-cell division efflux systems to antibiotic resistance and biofilm formation in Acinetobacter baumannii. MBio. 2015;6(2):6. DOI:10.1128/mBio.00309-15
  • Trebosc V, Gartenmann S, Royet K, et al. A novel genome-editing platform for drug-resistant Acinetobacter baumannii reveals an AdeR-unrelated tigecycline resistance mechanism. Antimicrob Agents Chemother. 2016;60(12):7263–7271. DOI:10.1128/AAC.01275-16
  • Trebosc V, Gartenmann S, Tötzl M, et al. Dissecting colistin resistance mechanisms in extensively drug-resistant Acinetobacter baumannii clinical isolates. MBio. 2019;10(4):10. DOI:10.1128/mBio.01083-19
  • Theuretzbacher U, Piddock LJV. Non-traditional antibacterial therapeutic options and challenges. Cell Host Microbe. 2019;26(1):61–72 doi:10.1016/j.chom.2019.06.004.
  • Wang N, Ozer EA, Mandel MJ, et al. Genome-wide identification of Acinetobacter baumannii genes necessary for persistence in the lung. MBio. 2014;5(3). e01163–14. DOI:10.1128/mBio.01163-14
  • Umland TC, Schultz LW, MacDonald U, et al. In vivo-validated essential genes identified in Acinetobacter baumannii by using human ascites overlap poorly with essential genes detected on laboratory media. MBio. 2012;3(4):3 doi:10.1128/mBio.00113-12.
  • Kaur N, Khokhar M, Jain V, et al. Identification of druggable targets for Acinetobacter baumannii via subtractive genomics and plausible inhibitors for MurA and MurB. Appl Biochem Biotechnol. 2013;171(2):417–436 doi:10.1007/s12010-013-0372-2.
  • Schwan WR. Survival of uropathogenic Escherichia coli in the murine urinary tract is dependent on OmpR. Microbiology. 2009;155(6):1832–1839 doi:10.1099/mic.0.026187-0.
  • Lucchini V, Sivignon A, Pieren M, et al. The role of OmpR in bile tolerance and pathogenesis of adherent-invasive Escherichia coli. Front Microbiol. 2021;12:684473 doi:10.3389/fmicb.2021.684473.
  • Singh S, Malik BK, Sharma DK. Molecular drug targets and structure based drug design: a holistic approach. Bioinformation. 2006;1(8):314–320 doi:10.6026/97320630001314.
  • Zgurskaya HI, López CA, Gnanakaran S. Permeability barrier of gram-negative cell envelopes and approaches to bypass it. ACS Infect Dis. 2015;1(11):512–522 doi:10.1021/acsinfecdis.5b00097.
  • Masi M, Réfregiers M, Pos KM, et al. Mechanisms of envelope permeability and antibiotic influx and efflux in gram-negative bacteria. Nat Microbiol. 2017;2(3):17001 doi:10.1038/nmicrobiol.2017.1.
  • Theuretzbacher U, Outterson K, Engel A, et al. The global preclinical antibacterial pipeline. Nat Rev Microbiol. 2020;18(5):275–285 doi:10.1038/s41579-019-0288-0.
  • Mydock-McGrane LK, Hannan TJ, Janetka JW. Rational design strategies for FimH antagonists: new drugs on the horizon for urinary tract infection and crohn’s disease. Expert Opin Drug Discov. 2017;12(7):711–731 doi:10.1080/17460441.2017.1331216.
  • Sarshar M, Behzadi P, Ambrosi C, et al. FimH and anti-adhesive therapeutics: a disarming strategy against uropathogens. Antibiotics. 2020;9(7):397 doi:10.3390/antibiotics9070397.
  • Schwan WR. Regulation of fim genes in uropathogenic Escherichia coli. World J Clin Infect Dis. 2011;1(1):17–25 doi:10.5495/wjcid.v1.i1.17.
  • Spaulding CN, Klein RD, Schreiber HL, et al. Precision antimicrobial therapeutics: the path of least resistance? NPJ Biofilms Microbiomes. 2018;4(1):1–7 doi:10.1038/s41522-018-0048-3.
  • Totsika M. Disarming pathogens: benefits and challenges of antimicrobials that target bacterial virulence instead of growth and viability. Future Med Chem. 2017;9(3):267–269 doi:10.4155/fmc-2016-0227.
  • Kammerer RA, Schulthess T, Landwehr R, et al. Tenascin-C hexabrachion assembly is a sequential two-step process initiated by coiled-coil α-helices. J Biol Chem. 1998;273(17):10602–10608 doi:10.1074/jbc.273.17.10602.
  • Emsley P, Lohkamp B, Scott W G and Cowtan K. (2010). Features and development of Coot. Acta Crystallogr D Biol CrystallogrActa Cryst DActa Cryst Sect DActa Crystallogr DActa Crystallogr Sect DActa Crystallogr Sect D Biol CrystallogrActa Crystallogr D Biol Cryst, 66(4), 486–501. doi:10.1107/S0907444910007493
  • Murshudov GN, Vagin AA, Dodson EJ. Refinement of Macromolecular Structures by the Maximum-Likelihood Method. Acta Crystallogr D Biol Crystallogr. 1997;53: 240–255. doi:10.1107/S0907444996012255
  • Biswas I, Machen A, Mettlach J. In Vitro motility assays for Acinetobacter species. Methods Mol Biol Clifton NJ. 2019;1946:177–187 doi:10.1007/978-1-4939-9118-1_17.
  • Schlatter S, Rimann M, Kelm J, et al. SAMY, a novel mammalian reporter gene derived from bacillus stearothermophilus α-amylase. Gene. 2002;282:19–31 doi:10.1016/S0378-1119(01)00824-1.