Untying the anchor for the lipopolysaccharide: lipid A structural modification systems offer diagnostic and therapeutic options to tackle polymyxin resistance
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
Velkov T, Thompson PE, Nation RL, Li J. Structure-activity relationships of polymyxin antibiotics. J Med Chem 2010;53:1898–916. doi: 10.1021/jm900999h.VelkovTThompsonPENationRLLiJ. Structure-activity relationships of polymyxin antibiotics. J Med Chem2010;53:1898–916. doi: 10.1021/jm900999hOpen DOISearch in Google Scholar
Li J, Nation RL, Milne RW, Turnidge JD, Coulthard K. Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria. Int J Antimicrob Agents 2005;25:11–25. doi: 10.1016/j.ijantimicag.2004.10.001LiJNationRLMilneRWTurnidgeJDCoulthardK. Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria. Int J Antimicrob Agents2005;25:11–25. doi: 10.1016/j.ijantimicag.2004.10.001Open DOISearch in Google Scholar
Ainsworth GC, Brown AM, Brownlee G. ‘Aerosporin’, an antibiotic produced by Bacillus aerosporus Greer. Nature 1947;160(4060):263. doi: 10.1038/160263a0AinsworthGCBrownAMBrownleeG. ‘Aerosporin’, an antibiotic produced by Bacillus aerosporus Greer. Nature1947;160(4060):263. doi:10.1038/160263a0Open DOISearch in Google Scholar
Vaara M. Polymyxins and their potential next generation as therapeutic antibiotics. Front Microbiol 2019;10:1689. doi: 10.3389/fmicb.2019.01689VaaraM. Polymyxins and their potential next generation as therapeutic antibiotics. Front Microbiol2019;10:1689. doi:10.3389/fmicb.2019.01689Open DOISearch in Google Scholar
Satlin MJ, Lewis JS, Weinstein MP, Patel J, Humphries RM, Kahlmeter G, Giske CG, Turnidge J. Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing position statements on Polymyxin B and colistin clinical breakpoints. Clin Infect Dis 2020;71(9):e523–9. doi: 10.1093/cid/ciaa121SatlinMJLewisJSWeinsteinMPPatelJHumphriesRMKahlmeterGGiskeCGTurnidgeJ. Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing position statements on Polymyxin B and colistin clinical breakpoints. Clin Infect Dis2020;71(9):e523–9. doi: 10.1093/cid/ciaa121Open DOISearch in Google Scholar
Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, Yu LF, Gu D, Ren H, Chen X, Lv L, He D, Zhou H, Liang Z, Liu JH, Shen J. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 2016;16:161–8. doi: 10.1016/S1473-3099(15)00424-7LiuYYWangYWalshTRYiLXZhangRSpencerJDoiYTianGDongBHuangXYuLFGuDRenHChenXLvLHeDZhouHLiangZLiuJHShenJ. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis2016;16:161–8. doi: 10.1016/S1473-3099(15)00424-7Open DOISearch in Google Scholar
Hamel M, Rolain JM, Baron SA. The history of colistin resistance mechanisms in bacteria: progress and challenges. Microorganisms 2021;9(2):442. doi: 10.3390/microorganisms9020442HamelMRolainJMBaronSA. The history of colistin resistance mechanisms in bacteria: progress and challenges. Microorganisms2021;9(2):442. doi:10.3390/microorganisms9020442Open DOISearch in Google Scholar
Gogry FA, Siddiqui MT, Sultan I, Rizwanul Haq QM. Current update on intrinsic and acquired colistin resistance mechanisms in bacteria. Front Med (Lausanne) 2021;8:677720. doi: 10.3389/fmed.2021.677720GogryFASiddiquiMTSultanIRizwanul HaqQM. Current update on intrinsic and acquired colistin resistance mechanisms in bacteria. Front Med (Lausanne)2021;8:677720. doi:10.3389/fmed.2021.677720Open DOISearch in Google Scholar
Wei W, Srinivas S, Lin J, Tang Z, Wang S, Ullah S, Kota VG, Feng Y. Defining ICR-Mo, an intrinsic colistin resistance determinant from Moraxella osloensis. PLOS Genet 2018;14(5):e1007389. doi: 10.1371/journal.pgen.1007389WeiWSrinivasSLinJTangZWangSUllahSKotaVGFengY. Defining ICR-Mo, an intrinsic colistin resistance determinant from Moraxella osloensis. PLOS Genet2018;14(5):e1007389. doi:10.1371/journal.pgen.1007389Open DOISearch in Google Scholar
Herrera CM, Hankins JV, Trent MS. Activation of PmrA inhibits LpxT-dependent phosphorylation of lipid A promoting resistance to antimicrobial peptides: Phosphorylation of lipid A inhibits pEtN addition. Mol Microbiol 2010;76:1444–60. doi: 10.1111/j.1365-2958.2010.07150.xHerreraCMHankinsJVTrentMS. Activation of PmrA inhibits LpxT-dependent phosphorylation of lipid A promoting resistance to antimicrobial peptides: Phosphorylation of lipid A inhibits pEtN addition. Mol Microbiol2010;76:1444–60. doi: 10.1111/j.1365-2958.2010.07150.xOpen DOISearch in Google Scholar
Needham BD, Trent MS. Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis. Nat Rev Microbiol 2013;11:467–81. doi: 10.1038/nrmicro3047NeedhamBDTrentMS. Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis. Nat Rev Microbiol2013;11:467–81. doi: 10.1038/nrmicro3047Open DOISearch in Google Scholar
Huang J, Li C, Song J, Velkov T, Wang L, Zhu Y, Li Y. Regulating polymyxin resistance in Gram-negative bacteria: roles of two-component systems PhoPQ and PmrAB. Future Microbiol 2020;15:445–59. doi: 10.2217/fmb-2019-0322HuangJLiCSongJVelkovTWangLZhuYLiY. Regulating polymyxin resistance in Gram-negative bacteria: roles of two-component systems PhoPQ and PmrAB. Future Microbiol2020;15:445–59. doi: 10.2217/fmb-2019-0322Open DOISearch in Google Scholar
Beceiro A, Llobet E, Aranda J, Bengoechea JA, Doumith M, Hornsey M, Dhanji H, Chart H, Bou G, Livermore DM, Woodford N. Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system. Antimicrob Agents Chemother 2011;55:3370–9. doi: 10.1128/AAC.00079-11BeceiroALlobetEArandaJBengoecheaJADoumithMHornseyMDhanjiHChartHBouGLivermoreDMWoodfordN. Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system. Antimicrob Agents Chemother2011;55:3370–9. doi: 10.1128/AAC.00079-11Open DOISearch in Google Scholar
Osei Sekyere J, Govinden U, Bester LA, Essack SY. Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods. J Appl Microbiol 2016;121:601–17. doi: 10.1111/jam.13169Osei SekyereJGovindenUBesterLAEssackSY. Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods. J Appl Microbiol2016;121:601–17. doi: 10.1111/jam.13169Open DOISearch in Google Scholar
Purcell AB, Voss BJ, Trent MS. Diacylglycerol kinase A is essential for polymyxin resistance provided by EptA, MCR-1, and other lipid A phosphoethanolamine transferases. J Bacteriol 2022;204(2):e00498–21. doi: 10.1128/jb.00498-21PurcellABVossBJTrentMS. Diacylglycerol kinase A is essential for polymyxin resistance provided by EptA, MCR-1, and other lipid A phosphoethanolamine transferases. J Bacteriol2022;204(2):e00498–21. doi: 10.1128/jb.00498-21Open DOISearch in Google Scholar
Xavier BB, Lammens C, Ruhal R, Kumar-Singh S, Butaye P, Goossens H, Malhotra-Kumar S. Identification of a novel plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016. Euro Sur veill 2016;21(27). doi: 10.2807/1560-7917.ES.2016.21.27.30280XavierBBLammensCRuhalRKumar-SinghSButayePGoossensHMalhotra-KumarS. Identification of a novel plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016. Euro Sur veill2016;21(27). doi: 10.2807/1560-7917.ES.2016.21.27.30280Open DOISearch in Google Scholar
AbuOun M, Stubberfield EJ, Duggett NA, Kirchner M, Dormer L, Nunez-Garcia J, Randall LP, Lemma F, Crook DW, Teale C, Smith RP, Anjum MF. mcr-1 and mcr-2 (mcr-6.1) variant genes identified in Moraxella species isolated from pigs in Great Britain from 2014 to 2015. J Antimicrob Chemother 2017;72:2745–9. doi: 10.1093/jac/dkx286AbuOunMStubberfieldEJDuggettNAKirchnerMDormerLNunez-GarciaJRandallLPLemmaFCrookDWTealeCSmithRPAnjumMF. mcr-1 and mcr-2 (mcr-6.1) variant genes identified in Moraxella species isolated from pigs in Great Britain from 2014 to 2015. J Antimicrob Chemother2017;72:2745–9. doi: 10.1093/jac/dkx286Open DOISearch in Google Scholar
Yin W, Li H, Shen Y, Liu Z, Wang S, Shen Z, Zhang R, Walsh TR, Shen J, Wang Y. Novel plasmid-mediated colistin resistance gene mcr-3 in Escherichia coli. mBio 2017;8(3):e00543–17. doi: 10.1128/mBio.00543-17YinWLiHShenYLiuZWangSShenZZhangRWalshTRShenJWangY. Novel plasmid-mediated colistin resistance gene mcr-3 in Escherichia coli. mBio2017;8(3):e00543–17. doi: 10.1128/mBio.00543-17Open DOISearch in Google Scholar
Borowiak M, Fischer J, Hammerl JA, Hendriksen RS, Szabo I, Malorny B. Identification of a novel transposon-associated phosphoethanolamine transferase gene, mcr-5, conferring colistin resistance in d-tartrate fermenting Salmonella enterica subsp. enterica serovar Paratyphi B. J Antimicrob Chemother 2017;72:3317–24. doi: 10.1093/jac/dkx327BorowiakMFischerJHammerlJAHendriksenRSSzaboIMalornyB. Identification of a novel transposon-associated phosphoethanolamine transferase gene, mcr-5, conferring colistin resistance in d-tartrate fermenting Salmonella enterica subsp. enterica serovar Paratyphi B. J Antimicrob Chemother2017;72:3317–24. doi: 10.1093/jac/dkx327Open DOISearch in Google Scholar
Carattoli A, Villa L, Feudi C, Curcio L, Orsini S, Luppi A, Pezzotti G, Magistrali CF. Novel plasmid-mediated colistin resistance mcr-4 gene in Salmonella and Escherichia coli, Italy 2013, Spain and Belgium, 2015 to 2016. Euro Surveill 2017;22(31):30589. doi: 10.2807/1560-7917.ES.2017.22.31.30589CarattoliAVillaLFeudiCCurcioLOrsiniSLuppiAPezzottiGMagistraliCF. Novel plasmid-mediated colistin resistance mcr-4 gene in Salmonella and Escherichia coli, Italy 2013, Spain and Belgium, 2015 to 2016. Euro Surveill2017;22(31):30589. doi:10.2807/1560-7917.ES.2017.22.31.30589Open DOISearch in Google Scholar
Wang X, Wang Y, Zhou Y, Li J, Yin W, Wang S, Zhang S, Shen J, Shen Z, Wang Y. Emergence of a novel mobile colistin resistance gene, mcr-8, in NDM-producing Klebsiella pneumoniae. Emerg Microbes Infect 2018;7(1):122. doi: 10.1038/s41426-018-0124-zWangXWangYZhouYLiJYinWWangSZhangSShenJShenZWangY. Emergence of a novel mobile colistin resistance gene, mcr-8, in NDM-producing Klebsiella pneumoniae. Emerg Microbes Infect2018;7(1):122. doi:10.1038/s41426-018-0124-zOpen DOISearch in Google Scholar
Wang C, Feng Y, Liu L, Wei L, Kang M, Zong Z. Identification of novel mobile colistin resistance gene mcr-10. Emerg Microbes Infect 2020;9:508–16. doi: 10.1080/22221751.2020.1732231WangCFengYLiuLWeiLKangMZongZ. Identification of novel mobile colistin resistance gene mcr-10. Emerg Microbes Infect2020;9:508–16. doi: 10.1080/22221751.2020.1732231Open DOISearch in Google Scholar
Yang YQ, Li YX, Lei CW, Zhang AY, Wang HN. Novel plasmid-mediated colistin resistance gene mcr-7.1 in Klebsiella pneumoniae. J Antimicrob Chemother 2018;73:1791–5. doi: 10.1093/jac/dky111YangYQLiYXLeiCWZhangAYWangHN. Novel plasmid-mediated colistin resistance gene mcr-7.1 in Klebsiella pneumoniae. J Antimicrob Chemother2018;73:1791–5. doi: 10.1093/jac/dky111Open DOISearch in Google Scholar
Carroll LM, Gaballa A, Guldimann C, Sullivan G, Henderson LO, Wiedmann M. Identification of novel mobilized colistin resistance gene mcr-9 in a multidrug-resistant, colistin-susceptible Salmonella enterica serotype Typhimurium isolate. mBio 2019;10(3):e00853–19. doi: 10.1128/mBio.00853-19CarrollLMGaballaAGuldimannCSullivanGHendersonLOWiedmannM. Identification of novel mobilized colistin resistance gene mcr-9 in a multidrug-resistant, colistin-susceptible Salmonella enterica serotype Typhimurium isolate. mBio2019;10(3):e00853–19. doi: 10.1128/mBio.00853-19Open DOISearch in Google Scholar
Campos MA, Vargas MA, Regueiro V, Llompart CM, Albertí S, Bengoechea JA. Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides. Infect Immun 2004;72:7107–14. doi: 10.1128/IAI.72.12.7107-7114.2004CamposMAVargasMARegueiroVLlompartCMAlbertíSBengoecheaJA. Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides. Infect Immun2004;72:7107–14. doi: 10.1128/IAI.72.12.7107-7114.2004Open DOISearch in Google Scholar
Padilla E, Llobet E, Doménech-Sánchez A, Martínez-Martínez L, Bengoechea JA, Albertí S. Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence. Antimicrob Agents Chemother 2010;54:177–83. doi: 10.1128/AAC.00715-09PadillaELlobetEDoménech-SánchezAMartínez-MartínezLBengoecheaJAAlbertíS. Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence. Antimicrob Agents Chemother2010;54:177–83. doi: 10.1128/AAC.00715-09Open DOISearch in Google Scholar
Mackenzie JS, Jeggo M. The One Health approach – Why is it so important? Trop Med Infect Dis 2019;4(2):88. doi: 10.3390/tropicalmed4020088MackenzieJSJeggoM. The One Health approach – Why is it so important?Trop Med Infect Dis2019;4(2):88. doi:10.3390/tropicalmed4020088Open DOISearch in Google Scholar
European Committee on Antimicrobial Susceptibility Testing (EUCAST). Clinical breakpoints – breakpoints and guidance [displayed 31 July 2023]. Available at https://www.eucast.org/clinical_breakpoints.European Committee on Antimicrobial Susceptibility Testing (EUCAST). Clinical breakpoints – breakpoints and guidance[displayed 31 July 2023]. Available at https://www.eucast.org/clinical_breakpoints.Search in Google Scholar
Liao W, Lin J, Jia H, Zhou C, Zhang Y, Lin Y, Ye J, Cao J, Zhou T. Resistance and heteroresistance to colistin in Escherichia coli isolates from Wenzhou, China. Infect Drug Resist 2020;13:3551–61. doi: 10.2147/IDR.S273784LiaoWLinJJiaHZhouCZhangYLinYYeJCaoJZhouT. Resistance and heteroresistance to colistin in Escherichia coli isolates from Wenzhou, China. Infect Drug Resist2020;13:3551–61. doi: 10.2147/IDR.S273784Open DOISearch in Google Scholar
Lin J, Xu C, Fang R, Cao J, Zhang X, Zhao Y, Dong G, Sun Y, Zhou T. Resistance and heteroresistance to colistin in Pseudomonas aeruginosa isolates from Wenzhou, China. Antimicrob Agents Chemother 2019;63(10):e00556–19. doi: 10.1128/AAC.00556-19LinJXuCFangRCaoJZhangXZhaoYDongGSunYZhouT. Resistance and heteroresistance to colistin in Pseudomonas aeruginosa isolates from Wenzhou, China. Antimicrob Agents Chemother2019;63(10):e00556–19. doi: 10.1128/AAC.00556-19Open DOISearch in Google Scholar
Chen L, Lin J, Lu H, Zhang X, Wang C, Liu H, Zhang X, Li J, Cao J, Zhou T. Deciphering colistin heteroresistance in Acinetobacter baumannii clinical isolates from Wenzhou, China. J Antibiot (Tokyo) 2020;73:463–70. doi: 10.1038/s41429-020-0289-2ChenLLinJLuHZhangXWangCLiuHZhangXLiJCaoJZhouT. Deciphering colistin heteroresistance in Acinetobacter baumannii clinical isolates from Wenzhou, China. J Antibiot (Tokyo)2020;73:463–70. doi: 10.1038/s41429-020-0289-2Open DOISearch in Google Scholar
Band VI, Crispell EK, Napier BA, Herrera CM, Tharp GK, Vavikolanu K, Pohl J, Read TD, Bosinger SE, Trent MS, Burd EM, Weiss DS. Antibiotic failure mediated by a resistant subpopulation in Enterobacter cloacae. Nat Microbiol 2016;1(6):16053. doi: 10.1038/nmicrobiol.2016.53BandVICrispellEKNapierBAHerreraCMTharpGKVavikolanuKPohlJReadTDBosingerSETrentMSBurdEMWeissDS. Antibiotic failure mediated by a resistant subpopulation in Enterobacter cloacae. Nat Microbiol2016;1(6):16053. doi:10.1038/nmicrobiol.2016.53Open DOISearch in Google Scholar
Hjort K, Nicoloff H, Andersson DI. Unstable tandem gene amplification generates heteroresistance (variation in resistance within a population) to colistin in Salmonella enterica. Mol Microbiol 2016;102:274–89. doi: 10.1111/mmi.13459HjortKNicoloffHAnderssonDI. Unstable tandem gene amplification generates heteroresistance (variation in resistance within a population) to colistin in Salmonella enterica. Mol Microbiol2016;102:274–89. doi: 10.1111/mmi.13459Open DOISearch in Google Scholar
Charretier Y, Diene SM, Baud D, Chatellier S, Santiago-Allexant E, van Belkum A, Guigon G, Schrenzel J. Colistin heteroresistance and involvement of the PmrAB regulatory system in Acinetobacter baumannii. Antimicrob Agents Chemother 2018;62(9):e00788–18. doi: 10.1128/AAC.00788-18CharretierYDieneSMBaudDChatellierSSantiago-AllexantEvan BelkumAGuigonGSchrenzelJ. Colistin heteroresistance and involvement of the PmrAB regulatory system in Acinetobacter baumannii. Antimicrob Agents Chemother2018;62(9):e00788–18. doi: 10.1128/AAC.00788-18Open DOISearch in Google Scholar
El-Halfawy OM, Valvano MA. Antimicrobial heteroresistance: an emerging field in need of clarity. Clin Microbiol Rev 2015;28:191–207. doi: 10.1128/CMR.00058-14El-HalfawyOMValvanoMA. Antimicrobial heteroresistance: an emerging field in need of clarity. Clin Microbiol Rev2015;28:191–207. doi: 10.1128/CMR.00058-14Open DOISearch in Google Scholar
Dortet L, Bonnin RA, Le Hello S, Fabre L, Bonnet R, Kostrzewa M, Filloux A, Larrouy-Maumus G. Detection of colistin resistance in Salmonella enterica using MALDIxin test on the routine MALDI biotyper sirius mass spectrometer. Front Microbiol 2020;11:1141. doi: 10.3389/fmicb.2020.01141DortetLBonninRALe HelloSFabreLBonnetRKostrzewaMFillouxALarrouy-MaumusG. Detection of colistin resistance in Salmonella enterica using MALDIxin test on the routine MALDI biotyper sirius mass spectrometer. Front Microbiol2020;11:1141. doi:10.3389/fmicb.2020.01141Open DOISearch in Google Scholar
Dortet L, Broda A, Bernabeu S, Glupczynski Y, Bogaerts P, Bonnin R, Naas T, Filloux A, Larrouy-Maumus G. Optimization of the MALDIxin test for the rapid identification of colistin resistance in Klebsiella pneumoniae using MALDI-TOF MS. J Antimicrob Chemother 2020;75:110–6. doi: 10.1093/jac/dkz405DortetLBrodaABernabeuSGlupczynskiYBogaertsPBonninRNaasTFillouxALarrouy-MaumusG. Optimization of the MALDIxin test for the rapid identification of colistin resistance in Klebsiella pneumoniae using MALDI-TOF MS. J Antimicrob Chemother2020;75:110–6. doi: 10.1093/jac/dkz405Open DOISearch in Google Scholar
Dortet L, Potron A, Bonnin RA, Plesiat P, Naas T, Filloux A, Larrouy-Maumus G. Rapid detection of colistin resistance in Acinetobacter baumannii using MALDI-TOF-based lipidomics on intact bacteria. Sci Rep 2018;8(1):16910. doi: 10.1038/s41598-018-35041-yDortetLPotronABonninRAPlesiatPNaasTFillouxALarrouy-MaumusG. Rapid detection of colistin resistance in Acinetobacter baumannii using MALDI-TOF-based lipidomics on intact bacteria. Sci Rep2018;8(1):16910. doi:10.1038/s41598-018-35041-yOpen DOISearch in Google Scholar
Jeannot K, Hagart K, Dortet L, Kostrzewa M, Filloux A, Plesiat P, Larrouy-Maumus G. Detection of colistin resistance in Pseudomonas aeruginosa using the MALDIxin test on the routine MALDI biotyper sirius mass spectrometer. Front Microbiol 2021;12:725383. doi: 10.3389/fmicb.2021.725383JeannotKHagartKDortetLKostrzewaMFillouxAPlesiatPLarrouy-MaumusG. Detection of colistin resistance in Pseudomonas aeruginosa using the MALDIxin test on the routine MALDI biotyper sirius mass spectrometer. Front Microbiol2021;12:725383. doi:10.3389/fmicb.2021.725383Open DOISearch in Google Scholar
Furniss RCD, Dortet L, Bolland W, Drews O, Sparbier K, Bonnin RA, Filloux A, Kostrzewa M, Mavridou DAI, Larrouy-Maumus G. Detection of colistin resistance in Escherichia coli by use of the MALDI biotyper sirius mass spectrometry system. J Clin Microbiol 2019;57(12):e01427–19. doi: 10.1128/JCM.01427-19FurnissRCDDortetLBollandWDrewsOSparbierKBonninRAFillouxAKostrzewaMMavridouDAILarrouy-MaumusG. Detection of colistin resistance in Escherichia coli by use of the MALDI biotyper sirius mass spectrometry system. J Clin Microbiol2019;57(12):e01427–19. doi: 10.1128/JCM.01427-19Open DOISearch in Google Scholar
Furniss RCD, Kostrzewa M, Mavridou DAI, Larrouy-Maumus G. The clue is in the lipid A: rapid detection of colistin resistance. PLOS Pathog 2020;16(4):e1008331. doi: 10.1371/journal.ppat.1008331FurnissRCDKostrzewaMMavridouDAILarrouy-MaumusG. The clue is in the lipid A: rapid detection of colistin resistance. PLOS Pathog2020;16(4):e1008331. doi:10.1371/journal.ppat.1008331Open DOISearch in Google Scholar
Sorensen M, Chandler CE, Gardner FM, Ramadan S, Khot PD, Leung LM, Farrance CE, Goodlett DR, Ernst RK, Nilsson E. Rapid microbial identification and colistin resistance detection via MALDI-TOF MS using a novel on-target extraction of membrane lipids. Sci Rep 2020;10(1):21536. doi: 10.1038/s41598-020-78401-3SorensenMChandlerCEGardnerFMRamadanSKhotPDLeungLMFarranceCEGoodlettDRErnstRKNilssonE. Rapid microbial identification and colistin resistance detection via MALDI-TOF MS using a novel on-target extraction of membrane lipids. Sci Rep2020;10(1):21536. doi:10.1038/s41598-020-78401-3Open DOISearch in Google Scholar
Smith RD, McElheny CL, Izac JR, Gardner FM, Chandler CE, Goodlett DR, Doi Y, Johnson JK, Ernst RK. A novel lipid-based MALDI-TOF assay for the rapid detection of colistin-resistant Enterobacter species. Microbiol Spectr 2022;10(1):e01445–21. doi: 10.1128/spectrum.01445-21SmithRDMcElhenyCLIzacJRGardnerFMChandlerCEGoodlettDRDoiYJohnsonJKErnstRK. A novel lipid-based MALDI-TOF assay for the rapid detection of colistin-resistant Enterobacter species. Microbiol Spectr2022;10(1):e01445–21. doi: 10.1128/spectrum.01445-21Open DOISearch in Google Scholar
Yang H, Smith RD, Chandler CE, Johnson JK, Jackson SN, Woods AS, Scott AJ, Goodlett DR, Ernst RK. Lipid A structural determination from a single colony. Anal Chem 2022;94:7460–5. doi: 10.1021/acs.analchem.1c05394YangHSmithRDChandlerCEJohnsonJKJacksonSNWoodsASScottAJGoodlettDRErnstRK. Lipid A structural determination from a single colony. Anal Chem2022;94:7460–5. doi: 10.1021/acs.analchem.1c05394Open DOISearch in Google Scholar
Leung LM, Cooper VS, Rasko DA, Guo Q, Pacey MP, McElheny CL, Mettus RT, Yoon SH, Goodlett DR, Ernst RK, Doi Y. Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae. J Antimicrob Chemother 2017;72:3035–42. doi: 10.1093/jac/dkx234LeungLMCooperVSRaskoDAGuoQPaceyMPMcElhenyCLMettusRTYoonSHGoodlettDRErnstRKDoiY. Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae. J Antimicrob Chemother2017;72:3035–42. doi: 10.1093/jac/dkx234Open DOISearch in Google Scholar
Dortet L, Bonnin RA, Pennisi I, Gauthier L, Jousset AB, Dabos L, Furniss RCD, Mavridou DAI, Bogaerts P, Glupczynski Y, Potron A, Plesiat P, Beyrouthy R, Robin F, Bonnet R, Naas T, Filloux A, Larrouy-Maumus G. Rapid detection and discrimination of chromosome- and MCR-plasmid-mediated resistance to polymyxins by MALDI-TOF MS in Escherichia coli: the MALDIxin test. J Antimicrob Chemother 2018;73:3359–67. doi: 10.1093/jac/dky330DortetLBonninRAPennisiIGauthierLJoussetABDabosLFurnissRCDMavridouDAIBogaertsPGlupczynskiYPotronAPlesiatPBeyrouthyRRobinFBonnetRNaasTFillouxALarrouy-MaumusG. Rapid detection and discrimination of chromosome- and MCR-plasmid-mediated resistance to polymyxins by MALDI-TOF MS in Escherichia coli: the MALDIxin test. J Antimicrob Chemother2018;73:3359–67. doi: 10.1093/jac/dky330Open DOISearch in Google Scholar
Bruker. MBT Lipid Xtract™ Kit [displayed 15 Jan 2023]. Available at https://www.bruker.com/en/products-and-solutions/microbiology-and-diagnostics/microbial-identification/mbt-lipid-xtract-kit.htmlBruker. MBT Lipid Xtract™ Kit[displayed 15 Jan 2023]. Available at https://www.bruker.com/en/products-and-solutions/microbiology-and-diagnostics/microbial-identification/mbt-lipid-xtract-kit.htmlSearch in Google Scholar
Dupuy FG, Pagano I, Andenoro K, Peralta MF, Elhady Y, Heinrich F, Tristram-Nagle S. Selective interaction of colistin with lipid model membranes. Biophys J 2018;114:919–28. doi: 10.1016/j.bpj.2017.12.027DupuyFGPaganoIAndenoroKPeraltaMFElhadyYHeinrichFTristram-NagleS. Selective interaction of colistin with lipid model membranes. Biophys J2018;114:919–28. doi: 10.1016/j.bpj.2017.12.027Open DOISearch in Google Scholar
Gogry FA, Siddiqui MT, Sultan I, Husain FM, Al-Kheraif AA, Ali A, Haq QMR. Colistin interaction and surface changes associated with mcr-1 conferred plasmid mediated resistance in E. coli and A. veronii strains. Phar maceutics 2022;14(2):295. doi: 10.3390/pharmaceutics14020295GogryFASiddiquiMTSultanIHusainFMAl-KheraifAAAliAHaqQMR. Colistin interaction and surface changes associated with mcr-1 conferred plasmid mediated resistance in E. coli and A. veronii strains. Phar maceutics2022;14(2):295. doi:10.3390/pharmaceutics14020295Open DOISearch in Google Scholar
Ma W, Jiang X, Dou Y, Zhang Z, Li J, Yuan B, Yang K. Biophysical impact of lipid A modification caused by mobile colistin resistance gene on bacterial outer membranes. J Phys Chem Lett 2021;12:11629–35. doi: 10.1021/acs.jpclett.1c03295MaWJiangXDouYZhangZLiJYuanBYangK. Biophysical impact of lipid A modification caused by mobile colistin resistance gene on bacterial outer membranes. J Phys Chem Lett2021;12:11629–35. doi: 10.1021/acs.jpclett.1c03295Open DOISearch in Google Scholar
Xu Y, Lin J, Cui T, Srinivas S, Feng Y. Mechanistic insights into transferable polymyxin resistance among gut bacteria. J Biol Chem 2018;293:4350–65. doi: 10.1074/jbc.RA117.000924XuYLinJCuiTSrinivasSFengY. Mechanistic insights into transferable polymyxin resistance among gut bacteria. J Biol Chem2018;293:4350–65. doi: 10.1074/jbc.RA117.000924Open DOISearch in Google Scholar
Hinchliffe P, Yang QE, Portal E, Young T, Li H, Tooke CL, Carvalho MJ, Paterson NG, Brem J, Niumsup PR, Tansawai U, Lei L, Li M, Shen Z, Wang Y, Schofield CJ, Mulholland AJ, Shen J, Fey N, Walsh TR, Spencer J. Insights into the mechanistic basis of plasmid-mediated colistin resistance from crystal structures of the catalytic domain of MCR-1. Sci Rep 2017;7:39392. doi: 10.1038/srep39392HinchliffePYangQEPortalEYoungTLiHTookeCLCarvalhoMJPatersonNGBremJNiumsupPRTansawaiULeiLLiMShenZWangYSchofieldCJMulhollandAJShenJFeyNWalshTRSpencerJ. Insights into the mechanistic basis of plasmid-mediated colistin resistance from crystal structures of the catalytic domain of MCR-1. Sci Rep2017;7:39392. doi:10.1038/srep39392Open DOISearch in Google Scholar
Hu M, Guo J, Cheng Q, Yang Z, Chan EWC, Chen S, Hao Q. Crystal structure of Escherichia coli originated MCR-1, a phosphoethanolamine transferase for colistin resistance. Sci Rep 2016;6:38793. doi: 10.1038/srep38793HuMGuoJChengQYangZChanEWCChenSHaoQ. Crystal structure of Escherichia coli originated MCR-1, a phosphoethanolamine transferase for colistin resistance. Sci Rep2016;6:38793. doi:10.1038/srep38793Open DOISearch in Google Scholar
Ma G, Zhu Y, Yu Z, Ahmad A, Zhang H. High resolution crystal structure of the catalytic domain of MCR-1. Sci Rep 2016;6:39540. doi: 10.1038/srep39540MaGZhuYYuZAhmadAZhangH. High resolution crystal structure of the catalytic domain of MCR-1. Sci Rep2016;6:39540. doi:10.1038/srep39540Open DOISearch in Google Scholar
Stojanoski V, Sankaran B, Prasad BVV, Poirel L, Nordmann P, Palzkill T. Structure of the catalytic domain of the colistin resistance enzyme MCR-1. BMC Biol 2016;14(1):81. doi: 10.1186/s12915-016-0303-0StojanoskiVSankaranBPrasadBVVPoirelLNordmannPPalzkillT. Structure of the catalytic domain of the colistin resistance enzyme MCR-1. BMC Biol2016;14(1):81. doi:10.1186/s12915-016-0303-0Open DOISearch in Google Scholar
Liu ZX, Han Z, Yu XL, Wen G, Zeng C. Crystal structure of the catalytic domain of MCR-1 (cMCR-1) in complex with d-xylose. Crystals 2018;8(4):172. doi: 10.3390/cryst8040172LiuZXHanZYuXLWenGZengC. Crystal structure of the catalytic domain of MCR-1 (cMCR-1) in complex with d-xylose. Crystals2018;8(4):172. doi:10.3390/cryst8040172Open DOISearch in Google Scholar
Lythell E, Suardíaz R, Hinchliffe P, Hanpaibool C, Visitsatthawong S, Oliveira ASF, Lang EJM, Surawatanawong P, Lee VS, Rungrotmongkol T, Fey N, Spencer J, Mulholland AJ. Resistance to the “last resort” antibiotic colistin: a single-zinc mechanism for phosphointermediate formation in MCR enzymes. Chem Commun 2020;56:6874–7. doi: 10.1039/D0CC02520HLythellESuardíazRHinchliffePHanpaiboolCVisitsatthawongSOliveiraASFLangEJMSurawatanawongPLeeVSRungrotmongkolTFeyNSpencerJMulhollandAJ. Resistance to the “last resort” antibiotic colistin: a single-zinc mechanism for phosphointermediate formation in MCR enzymes. Chem Commun2020;56:6874–7. doi: 10.1039/D0CC02520HOpen DOISearch in Google Scholar
Wei P, Song G, Shi M, Zhou Y, Liu Y, Lei J, Chen P, Yin L. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance. FASEB J 2018;32:1085–98. doi: 10.1096/fj.201700705RWeiPSongGShiMZhouYLiuYLeiJChenPYinL. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance. FASEB J2018;32:1085–98. doi: 10.1096/fj.201700705ROpen DOISearch in Google Scholar
Kai J, Wang S. Recent progress on elucidating the molecular mechanism of plasmid-mediated colistin resistance and drug design. Int Microbiol 2020;23:355–66. doi: 10.1007/s10123-019-00112-1KaiJWangS. Recent progress on elucidating the molecular mechanism of plasmid-mediated colistin resistance and drug design. Int Microbiol2020;23:355–66. doi: 10.1007/s10123-019-00112-1Open DOISearch in Google Scholar
Son SJ, Huang R, Squire CJ, Leung IKH. MCR-1: a promising target for structure-based design of inhibitors to tackle polymyxin resistance. Drug Discov Today 2019;24:206–16. doi: 10.1016/j.drudis.2018.07.004SonSJHuangRSquireCJLeungIKH. MCR-1: a promising target for structure-based design of inhibitors to tackle polymyxin resistance. Drug Discov Today2019;24:206–16. doi: 10.1016/j.drudis.2018.07.004Open DOISearch in Google Scholar
Zhou Y, Wang J, Guo Y, Liu X, Liu S, Niu X, Wang Y, Deng X. Discovery of a potential MCR-1 inhibitor that reverses polymyxin activity against clinical mcr-1-positive Enterobacteriaceae. J Infect 2019;78:364–72. doi: 10.1016/j.jinf.2019.03.004ZhouYWangJGuoYLiuXLiuSNiuXWangYDengX. Discovery of a potential MCR-1 inhibitor that reverses polymyxin activity against clinical mcr-1-positive Enterobacteriaceae. J Infect2019;78:364–72. doi: 10.1016/j.jinf.2019.03.004Open DOISearch in Google Scholar
Zhou Y, Wang T, Guo Y, Liu S, Wang J, Shen Y, Tang S, Wang Y, Deng X. In vitro/vivo activity of potential MCR-1 inhibitor in combination with colistin againsts mcr-1-positive Klebsiella pneumonia. Front Microbiol 2018;9:1615. doi: 10.3389/fmicb.2018.01615ZhouYWangTGuoYLiuSWangJShenYTangSWangYDengX. In vitro/vivo activity of potential MCR-1 inhibitor in combination with colistin againsts mcr-1-positive Klebsiella pneumonia. Front Microbiol2018;9:1615. doi:10.3389/fmicb.2018.01615Open DOISearch in Google Scholar
Zhou Y, Liu S, Wang T, Li H, Tang S, Wang J, Wang Y, Deng X. Pterostilbene, a potential MCR-1 inhibitor that enhances the efficacy of polymyxin B. Antimicrob Agents Chemother 2018;62(4):e02146–17. doi: 10.1128/AAC.02146-17ZhouYLiuSWangTLiHTangSWangJWangYDengX. Pterostilbene, a potential MCR-1 inhibitor that enhances the efficacy of polymyxin B. Antimicrob Agents Chemother2018;62(4):e02146–17. doi: 10.1128/AAC.02146-17Open DOISearch in Google Scholar
Liu X, Sun X, Deng X, Lv X, Wang J. Calycosin enhances the bactericidal efficacy of polymyxin B by inhibiting MCR-1 in vitro. J Appl Microbiol 2020;129:532–40. doi: 10.1111/jam.14635LiuXSunXDengXLvXWangJ. Calycosin enhances the bactericidal efficacy of polymyxin B by inhibiting MCR-1 in vitro. J Appl Microbiol2020;129:532–40. doi: 10.1111/jam.14635Open DOISearch in Google Scholar
Wang Y, Liu X, Sun X, Wen Z, Wang D, Peng L. A potential inhibitor of MCR-1: an attempt to enhance the efficacy of polymyxin against multidrug-resistant bacteria. Curr Microbiol 2020;77:3256–63. doi: 10.1007/s00284-020-02096-yWangYLiuXSunXWenZWangDPengL. A potential inhibitor of MCR-1: an attempt to enhance the efficacy of polymyxin against multidrug-resistant bacteria. Curr Microbiol2020;77:3256–63. doi: 10.1007/s00284-020-02096-yOpen DOISearch in Google Scholar
Xie S, Li L, Zhan B, Shen X, Deng X, Tan W, Fang T. Pogostone enhances the antibacterial activity of colistin against MCR-1-positive bacteria by inhibiting the biological function of MCR-1. Molecules 2022;27(9):2819. doi: 10.3390/molecules27092819XieSLiLZhanBShenXDengXTanWFangT. Pogostone enhances the antibacterial activity of colistin against MCR-1-positive bacteria by inhibiting the biological function of MCR-1. Molecules2022;27(9):2819. doi:10.3390/molecules27092819Open DOISearch in Google Scholar
Lan XJ, Yan HT, Lin F, Hou S, Li CC, Wang GS, Sun W, Xiao JH, Li S. Design, synthesis and biological evaluation of 1-phenyl-2-(phenylamino) ethanone derivatives as novel MCR-1 inhibitors. Molecules 2019;24(15):2719. doi: 10.3390/molecules24152719LanXJYanHTLinFHouSLiCCWangGSSunWXiaoJHLiS. Design, synthesis and biological evaluation of 1-phenyl-2-(phenylamino) ethanone derivatives as novel MCR-1 inhibitors. Molecules2019;24(15):2719. doi:10.3390/molecules24152719Open DOISearch in Google Scholar
Sun H, Zhang Q, Wang R, Wang H, Wong YT, Wang M, Hao Q, Yan A, Kao RY, Ho PL, Li H. Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin. Nat Commun 2020;11(1):5263. doi: 10.1038/s41467-020-18939-ySunHZhangQWangRWangHWongYTWangMHaoQYanAKaoRYHoPLLiH. Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin. Nat Commun2020;11(1):5263. doi:10.1038/s41467-020-18939-yOpen DOISearch in Google Scholar
Harris TL, Worthington RJ, Hittle LE, Zurawski DV, Ernst RK, Melander C. Small molecule downregulation of PmrAB reverses lipid A modification and breaks colistin resistance. ACS Chem Biol 2014;9:122–7. doi: 10.1021/cb400490kHarrisTLWorthingtonRJHittleLEZurawskiDVErnstRKMelanderC. Small molecule downregulation of PmrAB reverses lipid A modification and breaks colistin resistance. ACS Chem Biol2014;9:122–7. doi: 10.1021/cb400490kOpen DOISearch in Google Scholar
Brackett CM, Furlani RE, Anderson RG, Krishnamurthy A, Melander RJ, Moskowitz SM, Ernst RK, Melander C. Second generation modifiers of colistin resistance show enhanced activity and lower inherent toxicity. Tetrahedron 2016;72:3549–53. doi: 10.1016/j.tet.2015.09.019BrackettCMFurlaniREAndersonRGKrishnamurthyAMelanderRJMoskowitzSMErnstRKMelanderC. Second generation modifiers of colistin resistance show enhanced activity and lower inherent toxicity. Tetrahedron2016;72:3549–53. doi: 10.1016/j.tet.2015.09.019Open DOISearch in Google Scholar
Ghirga F, Stefanelli R, Cavinato L, Lo Sciuto A, Corradi S, Quaglio D, Calcaterra A, Casciaro B, Loffredo MR, Cappiello F, Morelli P, Antonelli A, Rossolini GM, Mangoni M, Mancone C, Botta B, Mori M, Ascenzioni F, Imperi F. A novel colistin adjuvant identified by virtual screening for ArnT inhibitors. J Antimicrob Chemother 2020;75:2564–72. doi: 10.1093/jac/dkaa200GhirgaFStefanelliRCavinatoLLo SciutoACorradiSQuaglioDCalcaterraACasciaroBLoffredoMRCappielloFMorelliPAntonelliARossoliniGMMangoniMManconeCBottaBMoriMAscenzioniFImperiF. A novel colistin adjuvant identified by virtual screening for ArnT inhibitors. J Antimicrob Chemother2020;75:2564–72. doi: 10.1093/jac/dkaa200Open DOISearch in Google Scholar
Quaglio D, Mangoni ML, Stefanelli R, Corradi S, Casciaro B, Vergine V, Lucantoni F, Cavinato L, Cammarone S, Loffredo MR, Cappiello F, Calcaterra A, Erazo S, Ghirga F, Mori M, Imperi F, Ascenzioni F, Botta B. ent-beyerane diterpenes as a key platform for the development of ArnT-mediated colistin resistance inhibitors. J Org Chem 2020;85:10891–901. doi: 10.1021/acs.joc.0c01459QuaglioDMangoniMLStefanelliRCorradiSCasciaroBVergineVLucantoniFCavinatoLCammaroneSLoffredoMRCappielloFCalcaterraAErazoSGhirgaFMoriMImperiFAscenzioniFBottaB. ent-beyerane diterpenes as a key platform for the development of ArnT-mediated colistin resistance inhibitors. J Org Chem2020;85:10891–901. doi: 10.1021/acs.joc.0c01459Open DOISearch in Google Scholar
Yao J, Rock CO. Phosphatidic acid synthesis in bacteria. Biochim Biophys Acta 2013;1831:495–502. doi: 10.1016/j.bbalip.2012.08.018YaoJRockCO. Phosphatidic acid synthesis in bacteria. Biochim Biophys Acta2013;1831:495–502. doi: 10.1016/j.bbalip.2012.08.018Open DOISearch in Google Scholar
May KL. Drown them in their own garbage: a new strategy to reverse polymyxin resistance? J Bacteriol 2022;204(2):e00574–21. doi: 10.1128/jb.00574-21MayKL. Drown them in their own garbage: a new strategy to reverse polymyxin resistance?J Bacteriol2022;204(2):e00574–21. doi: 10.1128/jb.00574-21Open DOISearch in Google Scholar
Barker WT, Nemeth AM, Brackett SM, Basak AK, Chandler CE, Jania LA, Zuercher WJ, Melander RJ, Koller BH, Ernst RK, Melander C. Repurposing eukaryotic kinase inhibitors as colistin adjuvants in Gram-negative bacteria. ACS Infect Dis 2019;5:1764–71. doi: 10.1021/acsinfecdis.9b00212BarkerWTNemethAMBrackettSMBasakAKChandlerCEJaniaLAZuercherWJMelanderRJKollerBHErnstRKMelanderC. Repurposing eukaryotic kinase inhibitors as colistin adjuvants in Gram-negative bacteria. ACS Infect Dis2019;5:1764–71. doi: 10.1021/acsinfecdis.9b00212Open DOISearch in Google Scholar
Hussein M, Schneider-Futschik EK, Paulin OKA, Allobawi R, Crawford S, Zhou QT, Hanif A, Baker M, Zhu Y, Li J, Velkov T. Effective strategy targeting polymyxin-resistant Gram-negative pathogens: polymyxin B in combination with the selective serotonin reuptake inhibitor sertraline. ACS Infect Dis 2020;6:1436–50. doi: 10.1021/acsinfecdis.0c00108HusseinMSchneider-FutschikEKPaulinOKAAllobawiRCrawfordSZhouQTHanifABakerMZhuYLiJVelkovT. Effective strategy targeting polymyxin-resistant Gram-negative pathogens: polymyxin B in combination with the selective serotonin reuptake inhibitor sertraline. ACS Infect Dis2020;6:1436–50. doi: 10.1021/acsinfecdis.0c00108Open DOISearch in Google Scholar