Mechanisms of antimicrobial resistance in Stenotrophomonas maltophilia: a review of current knowledge

References

• Esposito A, Pompilio A, Bettua C, et al. Evolution of Stenotrophomonas maltophilia in cystic fibrosis lung over chronic infection: a genomic and phenotypic population study. Front Microbiol. 2017;8:1590.
   PubMed Web of Science ®Google Scholar
• Brooke JS, Di Bonaventura G, Berg G, et al. Editorial: a multidisciplinary look at Stenotrophomonas maltophilia: an emerging multi-drug-resistant global opportunistic pathogen. Front Microbiol. 2017;8:1511.
   PubMed Web of Science ®Google Scholar
• Chang YT, Lin CY, Chen YH, et al. Update on infections caused by Stenotrophomonas maltophilia with particular attention to resistance mechanisms and therapeutic options. Front Microbiol. 2015;6:893.
   PubMed Web of Science ®Google Scholar
• Rello J, Kalwaje Eshwara V, Lagunes L, et al. A global priority list of the TOp TEn resistant microorganisms (TOTEM) study at intensive care: a prioritization exercise based on multi-criteria decision analysis. Eur J Clin Microbiol Infect Dis. 2019 Feb;38(2):319–323.
   PubMed Web of Science ®Google Scholar
• Berg G, Roskot N, Smalla K. Genotypic and phenotypic relationships between clinical and environmental isolates of Stenotrophomonas maltophilia. J Clin Microbiol. 1999 Nov;37(11):3594–3600.
   PubMed Web of Science ®Google Scholar
• Lecso-Bornet M, Pierre J, Sarkis-Karam D, et al. Susceptibility of Xanthomonas maltophilia to six quinolones and study of outer membrane proteins in resistant mutants selected in vitro. Antimicrob Agents Chemother. 1992 Mar;36(3):669–671.
   PubMed Web of Science ®Google Scholar
• Lira F, Berg G, Martinez JL. Double-face meets the bacterial world: the opportunistic pathogen Stenotrophomonas maltophilia. Front Microbiol. 2017;8:2190.
   PubMed Web of Science ®Google Scholar
• Youenou B, Favre-Bonte S, Bodilis J, et al. Comparative genomics of environmental and clinical Stenotrophomonas maltophilia strains with different antibiotic resistance profiles. Genome Biol Evol. 2015;7(9):2484–2505.
   PubMed Web of Science ®Google Scholar
• Wiehlmann L, Wagner G, Cramer N, et al. Population structure of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2007 May 8;104(19):8101–8106.
   PubMed Web of Science ®Google Scholar
• Morales G, Wiehlmann L, Gudowius P, et al. Structure of Pseudomonas aeruginosa populations analyzed by single nucleotide polymorphism and pulsed-field gel electrophoresis genotyping. J Bacteriol. 2004 July;186(13):4228–4237.
   PubMed Web of Science ®Google Scholar
• Alonso A, Rojo F, Martinez JL. Environmental and clinical isolates of Pseudomonas aeruginosa show pathogenic and biodegradative properties irrespective of their origin. Environ Microbiol. 1999 Oct;1(5):421–430.
   PubMed Web of Science ®Google Scholar
• Berg G, Martinez JL. Friends or foes: can we make a distinction between beneficial and harmful strains of the Stenotrophomonas maltophilia complex? [Perspective]. Front Microbiol. 2015 Mar 31;6:241.
   Web of Science ®Google Scholar
• Steinmann J, Mamat U, Abda EM, et al. Analysis of phylogenetic variation of Stenotrophomonas maltophilia reveals human-specific branches. Front Microbiol. 2018;9:806.
   PubMed Web of Science ®Google Scholar
• Lobo LJ, Tulu Z, Aris RM, et al. Pan-resistant Achromobacter xylosoxidans and Stenotrophomonas maltophilia infection in cystic fibrosis does not reduce survival after lung transplantation. Transplantation. 2015 Oct;99(10):2196–2202.
   PubMed Web of Science ®Google Scholar
• Ali U, Abbasi SA, Kaleem F, et al. Outbreak Of extensively drug resistant Stenotrophomonas maltophilia in burn unit. JAMC. 2017 Oct–Dec;29(4):686–688.
   Google Scholar
• Ibn Saied W, Merceron S, Schwebel C, et al. Ventilator-associated pneumonia due to Stenotrophomonas maltophilia: risk factors and outcome. J Infect. 2019 Nov 2..DOI: 10.1016/j.jinf.2019.10.021
   PubMedGoogle Scholar
• Hanes SD, Demirkan K, Tolley E, et al. Risk factors for late-onset nosocomial pneumonia caused by Stenotrophomonas maltophilia in critically ill trauma patients. Clin Infect Dis. 2002 Aug 1;35(3):228–235.
   PubMed Web of Science ®Google Scholar
• Wang CH, Lin JC, Chang FY, et al. Risk factors for hospital acquisition of trimethoprim-sulfamethoxazole resistant Stenotrophomonas maltophilia in adults: a matched case-control study. J Microbiol Immunol Infect. 2017 Oct;50(5):646–652.
   PubMedGoogle Scholar
• Adegoke AA, Stenstrom TA, Okoh AI. Stenotrophomonas maltophilia as an emerging ubiquitous pathogen: looking beyond contemporary antibiotic therapy. Front Microbiol. 2017;8:2276.
   PubMed Web of Science ®Google Scholar
• Hu LF, Chen GS, Kong QX, et al. Increase in the prevalence of resistance determinants to trimethoprim/sulfamethoxazole in clinical Stenotrophomonas maltophilia isolates in china. PloS One. 2016;11(6):e0157693.
   PubMed Web of Science ®Google Scholar
• Sanchez MB. Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia. Front Microbiol. 2015;6:658.
   PubMed Web of Science ®Google Scholar
• Crossman LC, Gould VC, Dow JM, et al. The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants. Genome Biol. 2008 Apr 17;9(4):R74.
   PubMed Web of Science ®Google Scholar
• Garcia-Leon G, Hernandez A, Hernando-Amado S, et al. A function of SmeDEF, the major quinolone resistance determinant of Stenotrophomonas maltophilia, is the colonization of plant roots. Appl Environ Microbiol. 2014 Aug;80(15):4559–4565.
   PubMed Web of Science ®Google Scholar
• Sanchez MB, Martinez JL. The efflux pump SmeDEF contributes to trimethoprim-sulfamethoxazole resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2015 July;59(7):4347–4348.
   PubMed Web of Science ®Google Scholar
• Zhao J, Liu Y, Liu Y, et al. Frequency and genetic determinants of tigecycline resistance in clinically isolated Stenotrophomonas maltophilia in Beijing, China. Front Microbiol. 2018;9:549.
   PubMed Web of Science ®Google Scholar
• Rahmati-Bahram A, Magee JT, Jackson SK. Temperature-dependent aminoglycoside resistance in Stenotrophomonas (Xanthomonas) maltophilia; alterations in protein and lipopolysaccharide with growth temperature. J Antimicrob Chemother. 1996 Apr;37(4):665–676.
   PubMed Web of Science ®Google Scholar
• Crowder MW, Walsh TR, Banovic L, et al. Overexpression, purification, and characterization of the cloned metallo-beta-lactamase L1 from Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 1998 Apr;42(4):921–926.
   PubMed Web of Science ®Google Scholar
• Walsh TR, MacGowan AP, Bennett PM. Sequence analysis and enzyme kinetics of the L2 serine beta-lactamase from Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 1997 July;41(7):1460–1464.
   PubMed Web of Science ®Google Scholar
• Okazaki A, Avison MB. Induction of L1 and L2 beta-lactamase production in Stenotrophomonas maltophilia is dependent on an AmpR-type regulator. Antimicrob Agents Chemother. 2008 Apr;52(4):1525–1528.
   PubMed Web of Science ®Google Scholar
• Lin CW, Huang YW, Hu RM, et al. The role of AmpR in regulation of L1 and L2 beta-lactamases in Stenotrophomonas maltophilia. Res Microbiol. 2009 Mar;160(2):152–158.
   PubMed Web of Science ®Google Scholar
• Hu RM, Huang KJ, Wu LT, et al. Induction of L1 and L2 beta-lactamases of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2008 Mar;52(3):1198–1200.
   PubMed Web of Science ®Google Scholar
• Lin CW, Hu RM, Huang SC, et al. Induction potential of clavulanic acid toward L1 and L2 beta-lactamases of Stenotrophomonas maltophilia. Eur J Clin Microbiol Infect Dis. 2008 Dec;27(12):1273–1275.
   PubMed Web of Science ®Google Scholar
• Huang YW, Hu RM, Lin CW, et al. NagZ-dependent and NagZ-independent mechanisms for beta-lactamase expression in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2012 Apr;56(4):1936–1941.
   PubMed Web of Science ®Google Scholar
• Alcaraz E, Garcia C, Friedman L, et al. The rpf/DSF signalling system of Stenotrophomonas maltophilia positively regulates biofilm formation, production of virulence-associated factors and beta-lactamase induction. FEMS Microbiol Lett. 2019 Mar 1;366(6):fnz069.
   PubMed Web of Science ®Google Scholar
• Yang TC, Huang YW, Hu RM, et al. AmpDI is involved in expression of the chromosomal L1 and L2 beta-lactamases of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2009 July;53(7):2902–2907.
   PubMed Web of Science ®Google Scholar
• Huang YW, Lin CW, Hu RM, et al. AmpN-AmpG operon is essential for expression of L1 and L2 beta-lactamases in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2010 June;54(6):2583–2589.
   PubMed Web of Science ®Google Scholar
• Jacobs C, Frere JM, Normark S. Cytosolic intermediates for cell wall biosynthesis and degradation control inducible beta-lactam resistance in gram-negative bacteria. Cell. 1997 Mar 21;88(6):823–832.
   PubMed Web of Science ®Google Scholar
• Lin CW, Lin HC, Huang YW, et al. Inactivation of mrcA gene derepresses the basal-level expression of L1 and L2 beta-lactamases in Stenotrophomonas maltophilia. J Antimicrob Chemother. 2011 Sept;66(9):2033–2037.
   PubMed Web of Science ®Google Scholar
• Huang YW, Wang Y, Lin Y, et al. Impacts of penicillin binding protein 2 inactivation on beta-lactamase expression and muropeptide profile in Stenotrophomonas maltophilia. mSystems. 2017 July–Aug;2(4)::e00077-17.
   PubMed Web of Science ®Google Scholar
• Dietz H, Pfeifle D, Wiedemann B. The signal molecule for beta-lactamase induction in Enterobacter cloacae is the anhydromuramyl-pentapeptide. Antimicrob Agents Chemother. 1997 Oct;41(10):2113–2120.
   PubMed Web of Science ®Google Scholar
• Mojica MF, Rutter JD, Taracila M, et al. Population structure, molecular epidemiology, and beta-lactamase diversity among Stenotrophomonas maltophilia isolates in the United States. mBio. 2019 July 2;10(4):e00405-19.
   PubMed Web of Science ®Google Scholar
• Lambert T, Ploy MC, Denis F, et al. Characterization of the chromosomal aac(6ʹ)-Iz gene of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 1999 Oct;43(10):2366–2371.
   PubMed Web of Science ®Google Scholar
• Li XZ, Zhang L, McKay GA, et al. Role of the acetyltransferase AAC(6ʹ)-Iz modifying enzyme in aminoglycoside resistance in Stenotrophomonas maltophilia. J Antimicrob Chemother. 2003 Apr;51(4):803–811.
   PubMed Web of Science ®Google Scholar
• Okazaki A, Avison MB. Aph(3ʹ)-IIc, an aminoglycoside resistance determinant from Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2007 Jan;51(1):359–360.
   PubMed Web of Science ®Google Scholar
• Tada T, Miyoshi-Akiyama T, Dahal RK, et al. Identification of a novel 6ʹ-N-aminoglycoside acetyltransferase, AAC(6ʹ)-Iak, from a multidrug-resistant clinical isolate of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2014 Oct;58(10):6324–6327.
   PubMed Web of Science ®Google Scholar
• Al-Hamad A, Upton M, Burnie J. Molecular cloning and characterization of SmrA, a novel ABC multidrug efflux pump from Stenotrophomonas maltophilia. J Antimicrob Chemother. 2009 Oct;64(4):731–734.
   PubMed Web of Science ®Google Scholar
• Lin YT, Huang YW, Liou RS, et al. MacABCsm, an ABC-type tripartite efflux pump of Stenotrophomonas maltophilia involved in drug resistance, oxidative and envelope stress tolerances and biofilm formation. J Antimicrob Chemother. 2014 Dec;69(12):3221–3226.
   PubMed Web of Science ®Google Scholar
• Huang YW, Hu RM, Chu FY, et al. Characterization of a major facilitator superfamily (MFS) tripartite efflux pump EmrCABsm from Stenotrophomonas maltophilia. J Antimicrob Chemother. 2013 Nov;68(11):2498–2505.
   PubMed Web of Science ®Google Scholar
• Alonso A, Martinez JL. Cloning and characterization of SmeDEF, a novel multidrug efflux pump from Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2000 Nov;44(11):3079–3086.
   PubMed Web of Science ®Google Scholar
• Zhang L, Li XZ, Poole K. SmeDEF multidrug efflux pump contributes to intrinsic multidrug resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2001 Dec;45(12):3497–3503.
   PubMed Web of Science ®Google Scholar
• Wu CJ, Lu HF, Lin YT, et al. Substantial contribution of SmeDEF, SmeVWX, SmQnr, and heat shock response to fluoroquinolone resistance in clinical isolates of Stenotrophomonas maltophilia. Front Microbiol. 2019;10:822.
   PubMed Web of Science ®Google Scholar
• Sanchez MB, Martinez JL. Overexpression of the efflux pumps SmeVWX and SmeDEF is a major cause of resistance to co-trimoxazole in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2018 June;62(6):e00301-18.
   Web of Science ®Google Scholar
• Sanchez P, Alonso A, Martinez JL. Cloning and characterization of SmeT, a repressor of the Stenotrophomonas maltophilia multidrug efflux pump SmeDEF. Antimicrob Agents Chemother. 2002 Nov;46(11):3386–3393.
   PubMed Web of Science ®Google Scholar
• Alonso A, Martinez JL. Expression of multidrug efflux pump SmeDEF by clinical isolates of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2001 June;45(6):1879–1881.
   PubMed Web of Science ®Google Scholar
• Sanchez P, Alonso A, Martinez JL. Regulatory regions of smeDEF in Stenotrophomonas maltophilia strains expressing different amounts of the multidrug efflux pump SmeDEF. Antimicrob Agents Chemother. 2004 June;48(6):2274–2276.
   PubMed Web of Science ®Google Scholar
• Hernandez A, Ruiz FM, Romero A, et al. The binding of triclosan to SmeT, the repressor of the multidrug efflux pump SmeDEF, induces antibiotic resistance in Stenotrophomonas maltophilia. PLoS Pathog. 2011 June;7(6):e1002103.
   PubMed Web of Science ®Google Scholar
• Sanchez P, Moreno E, Martinez JL. The biocide triclosan selects Stenotrophomonas maltophilia mutants that overproduce the SmeDEF multidrug efflux pump. Antimicrob Agents Chemother. 2005;49:781–782.
   PubMed Web of Science ®Google Scholar
• Blanco P, Corona F, Martinez JL. Involvement of the RND efflux pump transporter SmeH in the acquisition of resistance to ceftazidime in Stenotrophomonas maltophilia. Sci Rep. 2019 Mar 20; 9(1):4917.
   PubMedGoogle Scholar
• Gould VC, Okazaki A, Avison MB. Coordinate hyperproduction of SmeZ and SmeJK efflux pumps extends drug resistance in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2013 Jan;57(1):655–657.
   PubMed Web of Science ®Google Scholar
• Huang YW, Liou RS, Lin YT, et al. A linkage between SmeIJK efflux pump, cell envelope integrity, and sigmaE-mediated envelope stress response in Stenotrophomonas maltophilia. PloS One. 2014;9(11):e111784.
   PubMed Web of Science ®Google Scholar
• Lin CW, Huang YW, Hu RM, et al. SmeOP-TolCSm efflux pump contributes to the multidrug resistance of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2014;58(4):2405–2408.
   PubMed Web of Science ®Google Scholar
• Lin YT, Huang YW, Chen SJ, et al. The SmeYZ efflux pump of Stenotrophomonas maltophilia contributes to drug resistance, virulence-related characteristics, and virulence in mice. Antimicrob Agents Chemother. 2015 July;59(7):4067–4073.
   PubMed Web of Science ®Google Scholar
• Wu CJ, Huang YW, Lin YT, et al. Inactivation of SmeSyRy two-component regulatory system inversely regulates the expression of SmeYZ and SmeDEF efflux pumps in Stenotrophomonas maltophilia. PloS One. 2016;11(8):e0160943.
   PubMed Web of Science ®Google Scholar
• Sanchez MB, Martinez JL. SmQnr contributes to intrinsic resistance to quinolones in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2010 Jan;54(1):580–581.
   PubMed Web of Science ®Google Scholar
• Gordon NC, Wareham DW. Novel variants of the Smqnr family of quinolone resistance genes in clinical isolates of Stenotrophomonas maltophilia. J Antimicrob Chemother. 2010 Mar;65(3):483–489.
   PubMed Web of Science ®Google Scholar
• Kanamori H, Yano H, Tanouchi A, et al. Prevalence of Smqnr and plasmid-mediated quinolone resistance determinants in clinical isolates of Stenotrophomonas maltophilia from Japan: novel variants of Smqnr. New Microbes New Infect. 2015;7:8–14.
   PubMedGoogle Scholar
• Gracia-Paez JI, Ferraz JR, Silva IA, et al. Smqnr variants in clinical isolates of Stenotrophomonas maltophilia in Brazil. Rev Inst Med Trop Sao Paulo. 2013 Nov–Dec;55(6):417–420.
   PubMed Web of Science ®Google Scholar
• Wareham DW, Gordon NC, Shimizu K. Two new variants of and creation of a repository for Stenotrophomonas maltophilia quinolone protection protein (Smqnr) genes. Int J Antimicrob Agents. 2011 Jan;37(1):89–90.
   PubMed Web of Science ®Google Scholar
• Sanchez MB, Martinez JL. Regulation of Smqnr expression by SmqnrR is strain-specific in Stenotrophomonas maltophilia. J Antimicrob Chemother. 2015 Oct;70(10):2913–2914.
   PubMed Web of Science ®Google Scholar
• Fajardo A, Martinez-Martin N, Mercadillo M, et al. The neglected intrinsic resistome of bacterial pathogens. PloS One. 2008;3(2):e1619.
   PubMed Web of Science ®Google Scholar
• Martinez JL, Rojo F. Metabolic regulation of antibiotic resistance. FEMS Microbiol Rev. 2011 Sept;35(5):768–789.
   PubMed Web of Science ®Google Scholar
• Linares JF, Moreno R, Fajardo A, et al. The global regulator Crc modulates metabolism, susceptibility to antibiotics and virulence in Pseudomonas aeruginosa. Environ Microbiol. 2010 Dec;12(12):3196–3212.
   PubMed Web of Science ®Google Scholar
• Dalebroux ZD, Miller SI. Salmonellae PhoPQ regulation of the outer membrane to resist innate immunity. Curr Opin Microbiol. 2014 Feb;17:106–113.
   PubMed Web of Science ®Google Scholar
• Gooderham WJ, Hancock RE. Regulation of virulence and antibiotic resistance by two-component regulatory systems in Pseudomonas aeruginosa. FEMS Microbiol Rev. 2009 Mar;33(2):279–294.
   PubMed Web of Science ®Google Scholar
• Liu MC, Tsai YL, Huang YW, et al. Stenotrophomonas maltophilia PhoP, a two-component response regulator, involved in antimicrobial susceptibilities. PloS One. 2016;11(5):e0153753.
   PubMed Web of Science ®Google Scholar
• Hernando-Amado S, Blanco P, Alcalde-Rico M, et al. Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials. Drug Resist Updat. 2016;28:13–27.
   PubMed Web of Science ®Google Scholar
• Blair JM, Bavro VN, Ricci V, et al. AcrB drug-binding pocket substitution confers clinically relevant resistance and altered substrate specificity. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3511–3516.
   PubMed Web of Science ®Google Scholar
• Chang LL, Chen HF, Chang CY, et al. Contribution of integrons, and SmeABC and SmeDEF efflux pumps to multidrug resistance in clinical isolates of Stenotrophomonas maltophilia. J Antimicrob Chemother. 2004 Mar;53(3):518–521.
   PubMed Web of Science ®Google Scholar
• Li XZ, Zhang L, Poole K. SmeC, an outer membrane multidrug efflux protein of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2002 Feb;46(2):333–343.
   PubMed Web of Science ®Google Scholar
• Chen CH, Huang CC, Chung TC, et al. Contribution of resistance-nodulation-division efflux pump operon smeU1-V-W-U2-X to multidrug resistance of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2011 Dec;55(12):5826–5833.
   PubMed Web of Science ®Google Scholar
• Garcia-Leon G, Ruiz de Alegria Puig C, Garcia de la Fuente C, et al. High-level quinolone resistance is associated with the overexpression of smeVWX in Stenotrophomonas maltophilia clinical isolates. Clin Microbiol Infect. 2015 May;21(5):464–467.
   PubMed Web of Science ®Google Scholar
• Hernandez A, Mate MJ, Sanchez-Diaz PC, et al. Structural and functional analysis of SmeT, the Repressor of the Stenotrophomonas maltophilia multidrug efflux pump SmeDEF. J Biol Chem. 2009 May 22;284(21):14428–14438.
   PubMed Web of Science ®Google Scholar
• Ribera A, Domenech-Sanchez A, Ruiz J, et al. Mutations in gyrA and parC QRDRs are not relevant for quinolone resistance in epidemiological unrelated Stenotrophomonas maltophilia clinical isolates. Microbial Drug Resist (Larchmont, NY). 2002 Winter;8(4):245–251.
   PubMed Web of Science ®Google Scholar
• Valdezate S, Vindel A, Echeita A, et al. Topoisomerase II and IV quinolone resistance-determining regions in Stenotrophomonas maltophilia clinical isolates with different levels of quinolone susceptibility. Antimicrob Agents Chemother. 2002 Mar;46(3):665–671.
   PubMed Web of Science ®Google Scholar
• Jia W, Wang J, Xu H, et al. Resistance of Stenotrophomonas maltophilia to fluoroquinolones: prevalence in a university hospital and possible mechanisms. Int J Environ Res Public Health. 2015 May 13;12(5):5177–5195.
   PubMed Web of Science ®Google Scholar
• Blanco P, Corona F, Martinez JL. Mechanisms and phenotypic consequences of acquisition of tigecycline resistance by Stenotrophomonas maltophilia. J Antimicrob Chemother. 2019 Aug 1;74: 3221–3230.
   Web of Science ®Google Scholar
• Li LH, Zhang MS, Wu CJ, et al. Overexpression of SmeGH contributes to the acquired MDR of Stenotrophomonas maltophilia. J Antimicrob Chemother. 2019 Aug 1;74(8):2225–2229.
   PubMed Web of Science ®Google Scholar
• Garcia-Leon G, Salgado F, Oliveros JC, et al. Interplay between intrinsic and acquired resistance to quinolones in Stenotrophomonas maltophilia. Environ Microbiol. 2014 May;16(5):1282–1296.
   PubMed Web of Science ®Google Scholar
• Blair JM, Webber MA, Baylay AJ, et al. Molecular mechanisms of antibiotic resistance. Nature Rev Microbiol. 2015 Jan;13(1):42–51.
   PubMed Web of Science ®Google Scholar
• Falagas ME, Vouloumanou EK, Samonis G, et al. Fosfomycin. Clin Microbiol Rev. 2016 Apr;29(2):321–347.
   PubMed Web of Science ®Google Scholar
• Gil-Gil. T., Corona, F., Martínez JL, Bernardini A. The inactivation of enzymes belonging to the central carbon metabolism, a novel mechanism of developing antibiotic resistance. bioRxiv. 2019.
   Google Scholar
• Barbolla R, Catalano M, Orman BE, et al. Class 1 integrons increase trimethoprim-sulfamethoxazole MICs against epidemiologically unrelated Stenotrophomonas maltophilia isolates. Antimicrob Agents Chemother. 2004 Feb;48(2):666–669.
   PubMed Web of Science ®Google Scholar
• Toleman MA, Bennett PM, Bennett DM, et al. Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas maltophilia mediated by acquisition of sul genes. Emerg Infect Dis. 2007 Apr;13(4):559–565.
   PubMed Web of Science ®Google Scholar
• Hu LF, Chang X, Ye Y, et al. Stenotrophomonas maltophilia resistance to trimethoprim/sulfamethoxazole mediated by acquisition of sul and dfrA genes in a plasmid-mediated class 1 integron. Int J Antimicrob Agents. 2011 Mar;37(3):230–234.
   PubMed Web of Science ®Google Scholar
• Chung HS, Kim K, Hong SS, et al. The sul1 gene in Stenotrophomonas maltophilia with high-level resistance to trimethoprim/sulfamethoxazole. Ann Lab Med. 2015 Mar;35(2):246–249.
   PubMed Web of Science ®Google Scholar
• Hu LF, Xu XH, Yang HF, et al. Role of sul2 gene linked to transposase in resistance to trimethoprim/sulfamethoxazole among Stenotrophomonas maltophilia isolates. Ann Lab Med. 2016 Jan;36(1):73–75.
   PubMed Web of Science ®Google Scholar
• Furlan JPR, Sanchez DG, Gallo IFL, et al. Characterization of acquired antimicrobial resistance genes in environmental Stenotrophomonas maltophilia isolates from Brazil. Microbial Drug Resist (Larchmont, NY). 2019 May;25(4):475–479.
   PubMed Web of Science ®Google Scholar
• Zhang R, Sun Q, Hu YJ, et al. Detection of the Smqnr quinolone protection gene and its prevalence in clinical isolates of Stenotrophomonas maltophilia in China. J Med Microbiol. 2012 Apr;61(Pt 4):535–539.
   PubMed Web of Science ®Google Scholar
• Rizek CF, Jonas D, Garcia Paez JI, et al. Multidrug-resistant Stenotrophomonas maltophilia: description of new MLST profiles and resistance and virulence genes using whole-genome sequencing. J Glob Antimicrob Resist. 2018;15:212–214.
   PubMed Web of Science ®Google Scholar
• Margaritis A, Galani I, Chatzikonstantinou M, et al. Plasmid-mediated quinolone resistance determinants among Gram-negative bacteraemia isolates: a hidden threat. J Med Microbiol. 2017 Mar;66(3):266–275.
   PubMed Web of Science ®Google Scholar
• Hernando-Amado S, Coque TM, Baquero F, et al. Defining and combating antibiotic resistance from one health and global health perspectives. Nat Microbiol. 2019 Sept;4(9):1432–1442.
   PubMed Web of Science ®Google Scholar
• Li J, Liu S, Fu J, et al. Co-occurrence of colistin and meropenem resistance determinants in a Stenotrophomonas strain isolated from sewage water. Microbial Drug Resist (Larchmont, NY). 2019 Apr;25(3):317–325.
   PubMed Web of Science ®Google Scholar
• Fernandez L, Hancock RE. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev. 2012 Oct;25(4):661–681.
   PubMed Web of Science ®Google Scholar
• Fernandez L, Breidenstein EB, Hancock RE. Creeping baselines and adaptive resistance to antibiotics. Drug Resist Updat. 2011 Feb;14(1):1–21.
   PubMed Web of Science ®Google Scholar
• Balaban NQ, Merrin J, Chait R, et al. Bacterial persistence as a phenotypic switch. Science (New York, NY). 2004 Sept 10;305(5690):1622–1625.
   Google Scholar
• Mah TF, O’Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 2001 Jan;9(1):34–39.
   PubMed Web of Science ®Google Scholar
• Kubicek-Sutherland JZ, Heithoff DM, Ersoy SC, et al. Host-dependent induction of transient antibiotic resistance: a prelude to treatment failure. EBioMedicine. 2015 Sept;2(9):1169–1178.
   PubMed Web of Science ®Google Scholar
• Bonfiglio G, Livermore DM. Effect of media composition on the susceptibility of Xanthomonas maltophilia to beta-lactam antibiotics. J Antimicrob Chemother. 1991 Dec;28(6):837–842.
   PubMed Web of Science ®Google Scholar
• Hancock RE. Aminoglycoside uptake and mode of action–with special reference to streptomycin and gentamicin. I. Antagonists and mutants. J Antimicrob Chemother. 1981 Oct;8(4):249–276.
   PubMed Web of Science ®Google Scholar
• Martinez-Servat S, Yero D, Huedo P, et al. Heterogeneous colistin-resistance phenotypes coexisting in Stenotrophomonas maltophilia isolates influence colistin susceptibility testing. Front Microbiol. 2018;9:2871.
   PubMed Web of Science ®Google Scholar
• Rahmati-Bahram A, Magee JT, Jackson SK. Growth temperature-dependent variation of cell envelope lipids and antibiotic susceptibility in Stenotrophomonas (Xanthomonas) maltophilia. J Antimicrob Chemother. 1995 Aug;36(2):317–326.
   PubMed Web of Science ®Google Scholar
• Hall CW, Mah TF. Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol Rev. 2017 May 1;41(3):276–301.
   PubMed Web of Science ®Google Scholar
• Ryan RP, Fouhy Y, Garcia BF, et al. Interspecies signalling via the Stenotrophomonas maltophilia diffusible signal factor influences biofilm formation and polymyxin tolerance in Pseudomonas aeruginosa. Mol Microbiol. 2008 Apr;68(1):75–86.
   PubMed Web of Science ®Google Scholar
• Blanco P, Corona F, Martinez JL. Biolog phenotype microarray is a tool for the identification of multidrug resistance efflux pump inducers. Antimicrob Agents Chemother. 2018 Nov;62(11):e01263-18.
   Web of Science ®Google Scholar
• Sanchez MB, Decorosi F, Viti C, et al. Predictive studies suggest that the risk for the selection of antibiotic resistance by biocides is likely low in Stenotrophomonas maltophilia. PloS One. 2015;10(7):e0132816.
   PubMed Web of Science ®Google Scholar
• Bhargava HN, Leonard PA. Triclosan: applications and safety. Am J Infect Control. 1996 June;24(3):209–218.
   PubMed Web of Science ®Google Scholar
• Blanco P, Corona F, Sanchez MB, et al. Vitamin K3 induces the expression of the Stenotrophomonas maltophilia SmeVWX multidrug efflux pump. Antimicrob Agents Chemother. 2017 May;61(5):e02453-16.
   Web of Science ®Google Scholar
• Hu RM, Liao ST, Huang CC, et al. An inducible fusaric acid tripartite efflux pump contributes to the fusaric acid resistance in Stenotrophomonas maltophilia. PloS One. 2012;7(12):e51053.
   PubMed Web of Science ®Google Scholar
• Kaern M, Elston TC, Blake WJ, et al. Stochasticity in gene expression: from theories to phenotypes. Nat Rev Genet. 2005 June;6(6):451–464.
   PubMed Web of Science ®Google Scholar
• Abda EM, Krysciak D, Krohn-Molt I, et al. Phenotypic heterogeneity affects Stenotrophomonas maltophilia K279a colony morphotypes and beta-lactamase expression. Front Microbiol. 2015;6:1373.
   PubMed Web of Science ®Google Scholar
• Turrientes MC, Baquero MR, Sanchez MB, et al. Polymorphic mutation frequencies of clinical and environmental Stenotrophomonas maltophilia populations. Appl Environ Microbiol. 2010 Mar;76(6):1746–1758.
   PubMed Web of Science ®Google Scholar
• Falagas ME, Valkimadi PE, Huang YT, et al. Therapeutic options for Stenotrophomonas maltophilia infections beyond co-trimoxazole: a systematic review. J Antimicrob Chemother. 2008 Nov;62(5):889–894.
   PubMed Web of Science ®Google Scholar
• Tekce YT, Erbay A, Cabadak H, et al. Tigecycline as a therapeutic option in Stenotrophomonas maltophilia infections. J Chemother. 2012 June;24(3):150–154.
   PubMed Web of Science ®Google Scholar
• Wei C, Ni W, Cai X, et al. Evaluation of trimethoprim/sulfamethoxazole (SXT), minocycline, tigecycline, moxifloxacin, and ceftazidime alone and in combinations for SXT-susceptible and SXT-resistant Stenotrophomonas maltophilia by in vitro time-kill experiments. PloS One. 2016;11(3):e0152132.
   PubMed Web of Science ®Google Scholar
• Cho SY, Kang CI, Kim J, et al. Can levofloxacin be a useful alternative to trimethoprim-sulfamethoxazole for treating Stenotrophomonas maltophilia bacteremia? Antimicrob Agents Chemother. 2014;58(1):581–583.
   PubMed Web of Science ®Google Scholar
• Biagi M, Tan X, Wu T, et al. Activity of potential alternative treatment agents for Stenotrophomonas maltophilia isolates nonsusceptible to levofloxacin and/or trimethoprim-sulfamethoxazole. J Clin Microbiol. 2020 Jan 28;58(2):e01603-19.
   PubMedGoogle Scholar
• Garcia-Leon G, Salgado F, Oliveros JC, et al. Interplay between intrinsic and acquired resistance to quinolones in Stenotrophomonas maltophilia. Environ Microbiol. 2014 Jan;21(16):1282–1296.
   Google Scholar
• Gould VC, Avison MB. SmeDEF-mediated antimicrobial drug resistance in Stenotrophomonas maltophilia clinical isolates having defined phylogenetic relationships. J Antimicrob Chemother. 2006 June;57(6):1070–1076.
   PubMed Web of Science ®Google Scholar
• Hassan GS. Menadione. Profiles Drug Subst Excip Relat Methodol. 2013;38:227–313.
   PubMedGoogle Scholar
• Verrax J, Taper H, Buc Calderon P. Targeting cancer cells by an oxidant-based therapy. Curr Mol Pharmacol. 2008. 1. Jan(1):80–92.
   Google Scholar
• Rojas P, Garcia E, Calderon GM, et al. Successful treatment of Stenotrophomonas maltophilia meningitis in a preterm baby boy: a case report. J Med Case Rep. 2009 July;17(3):7389.
   Google Scholar
• Zelenitsky SA, Iacovides H, Ariano RE, et al. Antibiotic combinations significantly more active than monotherapy in an in vitro infection model of Stenotrophomonas maltophilia. Diagn Microbiol Infect Dis. 2005 Jan;51(1):39–43.
   PubMed Web of Science ®Google Scholar
• Ciacci N, Boncompagni S, Valzano F, et al. In vitro synergism of colistin and N-acetylcysteine against Stenotrophomonas maltophilia. Antibiotics (Basel). 2019 July 25;8(3):101.
   PubMed Web of Science ®Google Scholar
• García-León G, Sánchez MB, Martínez JL. The inactivation of intrinsic antibiotic resistance determinants widens the mutant selection window for quinolones of Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2012;2012;56:6397–6399.
   Web of Science ®Google Scholar
• Sánchez P, Le U, Martínez JL. The efflux pump inhibitor Phe-Arg-β-naphthylamide does not abolish the activity of the Stenotrophomonas maltophilia SmeDEF multidrug efflux pump. J Antimicrob Chemother. 2003;51(4):1042–1045.
   PubMed Web of Science ®Google Scholar
• Al-Hamad A, Burnie J, Upton M. Enhancement of antibiotic susceptibility of Stenotrophomonas maltophilia using a polyclonal antibody developed against an ABC multidrug efflux pump. Can J Microbiol. 2011 Oct;57(10):820–828.
   PubMed Web of Science ®Google Scholar
• Venkatesha SH, Moudgil KD. Celastrol and its role in controlling chronic diseases. Adv Exp Med Biol. 2016;928:267–289.
   PubMed Web of Science ®Google Scholar
• Kim HR, Lee D, Eom YB. Anti-biofilm and anti-virulence efficacy of celastrol against Stenotrophomonas maltophilia. Int J Med Sci. 2018;15(6):617–627.
   PubMed Web of Science ®Google Scholar
• Defoirdt T. Quorum-sensing systems as targets for antivirulence therapy. Trends Microbiol. 2018 Apr;26(4):313–328.
   PubMed Web of Science ®Google Scholar
• Scoffone VC, Trespidi G, Chiarelli LR, et al. Quorum sensing as antivirulence target in cystic fibrosis pathogens. Int J Mol Sci. 2019 Apr 13;20(8):1838.
   PubMed Web of Science ®Google Scholar
• Huedo P, Yero D, Martinez-Servat S, et al. Decoding the genetic and functional diversity of the DSF quorum-sensing system in Stenotrophomonas maltophilia. Front Microbiol. 2015;6:761.
   PubMed Web of Science ®Google Scholar