Molecular mechanisms of antibiotic resistance (original) (raw)

• Walker, D. & Fowler, T. Annual Report of the Chief Medical Officer: Volume Two, 2011: Infections and the Rise of Antimicrobial Resistance (Department of Health, 2011).
  Google Scholar
• World Economic Forum. Global Risks 2013 — Eighth Edition http://www.weforum.org/reports/global-risks-2013-eighth-edition (2013).
• World Economic Forum. Global Risks 2014 Report http://www.weforum.org/reports/global-risks-2014-report (2014).
• World Health Organization. Antimicrobial Resistance: Global Report on Surveillance 2014 http://www.who.int/drugresistance/documents/surveillancereport/en/ (2014).
• Hampton, T. Report reveals scope of US antibiotic resistance threat. JAMA 310, 1661–1663 (2013).
  Article CAS PubMed Google Scholar
• Chuanchuen, R., Karkhoff-Schweizer, R. R. & Schweizer, H. P. High-level triclosan resistance in Pseudomonas aeruginosa is solely a result of efflux. Am. J. Infect. Control 31, 124–127 (2003).
  Article PubMed Google Scholar
• Zhu, L., Lin, J., Ma, J., Cronan, J. E. & Wang, H. Triclosan resistance of Pseudomonas aeruginosa PAO1 is due to FabV, a triclosan-resistant enoyl-acyl carrier protein reductase. Antimicrob. Agents Chemother. 54, 689–698 (2010).
  Article CAS PubMed Google Scholar
• Randall, C. P., Mariner, K. R., Chopra, I. & O'Neill, A. J. The target of daptomycin is absent from Escherichia coli and other Gram-negative pathogens. Antimicrob. Agents Chemother. 57, 637–639 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Tsuchido, T. & Takano, M. Sensitization by heat treatment of Escherichia coli K-12 cells to hydrophobic antibacterial compounds. Antimicrob. Agents Chemother. 32, 1680–1683 (1988).
  Article CAS PubMed PubMed Central Google Scholar
• Blake, K. L. & O'Neill, A. J. Transposon library screening for identification of genetic loci participating in intrinsic susceptibility and acquired resistance to antistaphylococcal agents. J. Antimicrob. Chemother. 68, 12–16 (2013).
  Article CAS PubMed Google Scholar
• Liu, A. et al. Antibiotic sensitivity profiles determined with an Escherichia coli gene knockout collection: generating an antibiotic bar code. Antimicrob. Agents Chemother. 54, 1393–1403 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Barbee, L. A., Soge, O. O., Holmes, K. K. & Golden, M. R. In vitro synergy testing of novel antimicrobial combination therapies against Neisseria gonorrhoeae. J. Antimicrob. Chemother. 69, 1572–1578 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Hornsey, M., Longshaw, C., Phee, L. & Wareham, D. W. In vitro activity of telavancin in combination with colistin versus Gram-negative bacterial pathogens. Antimicrob. Agents Chemother. 56, 3080–3085 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Principe, L. et al. In vitro activity of doripenem in combination with various antimicrobials against multidrug-resistant Acinetobacter baumannii: possible options for the treatment of complicated infection. Microb. Drug Resist. 19, 407–414 (2013).
  Article CAS PubMed Google Scholar
• Fernández, L. & Hancock, R. E. W. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin. Microbiol. Rev. 25, 661–681 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Nikaido, H. Multidrug resistance in bacteria. Annu. Rev. Biochem. 78, 119–146 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Wright, G. D. Molecular mechanisms of antibiotic resistance. Chem. Commun. 47, 4055–4061 (2011).
  Article CAS Google Scholar
• Kojima, S. & Nikaido, H. Permeation rates of penicillins indicate that Escherichia coli porins function principally as nonspecific channels. Proc. Natl Acad. Sci. USA 110, E2629–E2634 (2013).
  Article PubMed PubMed Central Google Scholar
• Vargiu, A. V. & Nikaido, H. Multidrug binding properties of the AcrB efflux pump characterized by molecular dynamics simulations. Proc. Natl Acad. Sci. USA 109, 20637–20642 (2012).
  Article PubMed PubMed Central Google Scholar
• Tran, Q. T., Williams, S., Farid, R., Erdemli, G. & Pearlstein, R. The translocation kinetics of antibiotics through porin OmpC: insights from structure-based solvation mapping using WaterMap. Proteins 81, 291–299 (2013).
  Article CAS PubMed Google Scholar
• Tamber, S. & Hancock, R. E. On the mechanism of solute uptake in Pseudomonas. Front. Biosci. 8, s472–s483 (2003).
  Article CAS PubMed Google Scholar
• Baroud, M. et al. Underlying mechanisms of carbapenem resistance in extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Escherichia coli isolates at a tertiary care centre in Lebanon: role of OXA-48 and NDM-1 carbapenemases. Int. J. Antimicrob. Agents 41, 75–79 (2013).
  Article CAS PubMed Google Scholar
• Lavigne, J. P. et al. An adaptive response of Enterobacter aerogenes to imipenem: regulation of porin balance in clinical isolates. Int. J. Antimicrob. Agents 41, 130–136 (2013).
  Article CAS PubMed Google Scholar
• Poulou, A. et al. Outbreak caused by an ertapenem-resistant, CTX-M-15-producing Klebsiella pneumoniae sequence type 101 clone carrying an OmpK36 porin variant. J. Clin. Microbiol. 51, 3176–3182 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Wozniak, R. A. & Waldor, M. K. Integrative and conjugative elements: mosaic mobile genetic elements enabling dynamic lateral gene flow. Nature Rev. Microbiol. 8, 552–563 (2010).
  Article CAS Google Scholar
• Wozniak, A. et al. Porin alterations present in non-carbapenemase-producing Enterobacteriaceae with high and intermediate levels of carbapenem resistance in Chile. J. Med. Microbiol. 61, 1270–1279 (2012).
  Article CAS PubMed Google Scholar
• Novais, Â. et al. Spread of an OmpK36-modified ST15 Klebsiella pneumoniae variant during an outbreak involving multiple carbapenem-resistant Enterobacteriaceae species and clones. Eur. J. Clin. Microbiol. Infecti. Dis. 31, 3057–3063 (2012).
  Article CAS Google Scholar
• Tangden, T., Adler, M., Cars, O., Sandegren, L. & Lowdin, E. Frequent emergence of porin-deficient subpopulations with reduced carbapenem susceptibility in ESBL-producing Escherichia coli during exposure to ertapenem in an in vitro pharmacokinetic model. J. Antimicrob. Chemother. 68, 1319–1326 (2013).
  Article CAS PubMed Google Scholar
• Papagiannitsis, C. C. et al. OmpK35 and OmpK36 porin variants associated with specific sequence types of Klebsiella pneumoniae. J. Chemother. 25, 250–254 (2013).
  Article CAS PubMed Google Scholar
• Floyd, J. L., Smith, K. P., Kumar, S. H., Floyd, J. T. & Varela, M. F. LmrS is a multidrug efflux pump of the major facilitator superfamily from Staphylococcus aureus. Antimicrob. Agents Chemother. 54, 5406–5412 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Hu, R. M., Liao, S. T., Huang, C. C., Huang, Y. W. & Yang, T. C. An inducible fusaric acid tripartite efflux pump contributes to the fusaric acid resistance in Stenotrophomonas maltophilia. PLoS ONE 7, e51053 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Kim, C. et al. The mechanism of heterogeneous β-lactam resistance in MRSA: key role of the stringent stress response. PLoS ONE 8, e82814 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Ogawa, W., Onishi, M., Ni, R., Tsuchiya, T. & Kuroda, T. Functional study of the novel multidrug efflux pump KexD from Klebsiella pneumoniae. Gene 498, 177–182 (2012).
  Article CAS PubMed Google Scholar
• Dolejska, M., Villa, L., Poirel, L., Nordmann, P. & Carattoli, A. Complete sequencing of an IncHI1 plasmid encoding the carbapenemase NDM-1, the ArmA 16S RNA methylase and a resistance nodulation cell division/multidrug efflux pump. J. Antimicrob. Chemother. 68, 34–39 (2013).
  Article CAS PubMed Google Scholar
• Piddock, L. J. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin. Microbiol. Rev. 19, 382–402 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Hinchliffe, P., Symmons, M. F., Hughes, C. & Koronakis, V. Structure and operation of bacterial tripartite pumps. Annu. Rev. Microbiol. 67, 221–242 (2013).
  Article CAS PubMed Google Scholar
• Ruggerone, P., Murakami, S., Pos, K. M. & Vargiu, A. V. RND efflux pumps: structural information translated into function and inhibition mechanisms. Curr. Top. Med. Chem. 13, 3079–3100 (2013).
  Article CAS PubMed Google Scholar
• Eicher, T. et al. Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop. Proc. Natl Acad. Sci. USA 109, 5687–5692 (2012).
  Article PubMed PubMed Central Google Scholar
• Hung, L.-W. et al. Crystal structure of AcrB complexed with linezolid at 3.5 Å resolution. J. Struct. Funct. Genom. 14, 71–75 (2013).
  Article CAS Google Scholar
• Murakami, S., Nakashima, R., Yamashita, E., Matsumoto, T. & Yamaguchi, A. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443, 173–179 (2006).
  Article CAS PubMed Google Scholar
• Nakashima, R., Sakurai, K., Yamasaki, S., Nishino, K. & Yamaguchi, A. Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket. Nature 480, 565–569 (2011).
  Article CAS PubMed Google Scholar
• Su, C.-C. et al. Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli. Nature 470, 558–562 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Du, D. et al. Structure of the AcrAB-TolC multidrug efflux pump. Nature 509, 512–515 (2014). This article describes the first structure based on data from a complete tripartite efflux system and determines the stoichiometry of the system and key interactions between residues.
  Article CAS PubMed PubMed Central Google Scholar
• Symmons, M. F., Bokma, E., Koronakis, E., Hughes, C. & Koronakis, V. The assembled structure of a complete tripartite bacterial multidrug efflux pump. Proc. Natl Acad. Sci. USA 106, 7173–7178 (2009).
  Article PubMed PubMed Central Google Scholar
• Janganan, T. K., Bavro, V. N., Zhang, L., Borges-Walmsley, M. I. & Walmsley, A. R. Tripartite efflux pumps: energy is required for dissociation, but not assembly or opening of the outer membrane channel of the pump. Mol. Microbiol. 88, 590–602 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Janganan, T. K. et al. Evidence for the assembly of a bacterial tripartite multidrug pump with a stoichiometry of 3:6:3. J. Biol. Chem. 286, 26900–26912 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Stegmeier, J. F., Polleichtner, G., Brandes, N., Hotz, C. & Andersen, C. Importance of the adaptor (membrane fusion) protein hairpin domain for the functionality of multidrug efflux pumps. Biochemistry 45, 10303–10312 (2006).
  Article CAS PubMed Google Scholar
• Yum, S. et al. Crystal structure of the periplasmic component of a tripartite macrolide-specific efflux pump. J. Mol. Biol. 387, 1286–1297 (2009).
  Article CAS PubMed Google Scholar
• Everett, M. J., Jin, Y. F., Ricci, V. & Piddock, L. J. Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. Antimicrob. Agents Chemother. 40, 2380–2386 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Kosmidis, C. et al. Expression of multidrug resistance efflux pump genes in clinical and environmental isolates of Staphylococcus aureus. Int. J. Antimicrob. Agents 40, 204–209 (2012).
  Article CAS PubMed Google Scholar
• Pumbwe, L. & Piddock, L. J. V. Two efflux systems expressed simultaneously in multidrug-resistant Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 44, 2861–2864 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Zalucki, Y. M., Dhulipala, V. & Shafer, W. M. Dueling regulatory properties of a transcriptional activator (MtrA) and repressor (MtrR) that control efflux pump gene expression in Neisseria gonorrhoeae. mBio 3, e00446-12 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Bailey, A. M. et al. RamA, a member of the AraC/XylS family, influences both virulence and efflux in Salmonella enterica serovar Typhimurium. J. Bacteriol. 192, 1607–1616 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Abouzeed, Y. M., Baucheron, S. & Cloeckaert, A. ramR mutations involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium. Antimicrob. Agents Chemother. 52, 2428–2434 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Alekshun, M. N. & Levy, S. B. Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon. Antimicrob. Agents Chemother. 41, 2067–2075 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Baucheron, S. et al. ramR mutations affecting fluoroquinolone susceptibility in epidemic multidrug-resistant salmonella enterica serovar kentucky ST198. Front. Microbiol. 4, 213 (2013).
  Article PubMed PubMed Central Google Scholar
• Baucheron, S. et al. Bile-mediated activation of the acrAB and tolC multidrug efflux genes occurs mainly through transcriptional derepression of ramA in Salmonella enterica serovar Typhimurium. J. Antimicrob. Chemother. 69, 2400–2406 (2014).
  Article CAS PubMed Google Scholar
• Schindler, B. D. et al. Functional consequences of substitution mutations in MepR, a repressor of the Staphylococcus aureus mepA multidrug efflux pump gene. J. Bacteriol. 195, 3651–3662 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Pomposiello, P. J., Bennik, M. H. & Demple, B. Genome-wide transcriptional profiling of the Escherichia coli responses to superoxide stress and sodium salicylate. J. Bacteriol. 183, 3890–3902 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Kaatz, G. W., Thyagarajan, R. V. & Seo, S. M. Effect of promoter region mutations and mgrA overexpression on transcription of norA, which encodes a Staphylococcus aureus multidrug efflux transporter. Antimicrob. Agents Chemother. 49, 161–169 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Kaczmarek, F. S. et al. Genetic and molecular characterization of β-lactamase-negative ampicillin-resistant Haemophilus influenzae with unusually high resistance to ampicillin. Antimicrob. Agents Chemother. 48, 1630–1639 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Olliver, A., Vallé, M., Chaslus-Dancla, E. & Cloeckaert, A. Role of an acrR mutation in multidrug resistance of _in vitro_-selected fluoroquinolone-resistant mutants of Salmonella enterica serovar Typhimurium. FEMS Microbiol. Lett. 238, 267–272 (2004).
  CAS PubMed Google Scholar
• van der Straaten, T., Janssen, R., Mevius, D. J. & van Dissel, J. T. Salmonella gene rma (ramA) and multiple-drug-resistant Salmonella enterica serovar typhimurium. Antimicrob. Agents Chemother. 48, 2292–2294 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Warner, D. M., Shafer, W. M. & Jerse, A. E. Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC–MtrD–MtrE efflux pump system confer different levels of antimicrobial resistance and in vivo fitness. Mol. Microbiol. 70, 462–478 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Webber, M. A. & Piddock, L. J. V. Absence of mutations in marRAB or soxRS in _acrB_-overexpressing fluoroquinolone-resistant clinical and veterinary isolates of Escherichia coli. Antimicrob. Agents Chemother. 45, 1550–1552 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Webber, M. A., Talukder, A. & Piddock, L. J. V. Contribution of mutation at amino acid 45 of AcrR to acrB expression and ciprofloxacin resistance in clinical and veterinary Escherichia coli Isolates. Antimicrob. Agents Chemother. 49, 4390–4392 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Hirakawa, H., Inazumi, Y., Masaki, T., Hirata, T. & Yamaguchi, A. Indole induces the expression of multidrug exporter genes in Escherichia coli. Mol. Microbiol. 55, 1113–1126 (2005).
  Article CAS PubMed Google Scholar
• Nikaido, E. et al. Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genome-wide analyses. Gut Pathog. 4, 5 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Nikaido, E., Shirosaka, I., Yamaguchi, A. & Nishino, K. Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat. Microbiology 157, 648–655 (2011).
  Article CAS PubMed Google Scholar
• Deng, X. et al. Expression of multidrug resistance efflux pump gene norA is iron responsive in Staphylococcus aureus. J. Bacteriol. 194, 1753–1762 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Mercante, A. D. et al. MpeR regulates the mtr efflux locus in Neisseria gonorrhoeae and modulates antimicrobial resistance by an iron-responsive mechanism. Antimicrob. Agents Chemother. 56, 1491–1501 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, K. et al. The expression of ABC efflux pump, Rv1217c–Rv1218c, and its association with multidrug resistance of Mycobacterium tuberculosis in China. Curr. Microbiol. 66, 222–226 (2013).
  Article CAS PubMed Google Scholar
• Kumar, N. et al. Crystal structure of the transcriptional regulator Rv1219c of Mycobacterium tuberculosis. Protein Sci. 23, 423–432 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Yamasaki, S. et al. The crystal structure of multidrug-resistance regulator RamR with multiple drugs. Nature Commun. 4, 2078 (2013).
  Article CAS Google Scholar
• Billal, D. S., Feng, J., Leprohon, P., Legare, D. & Ouellette, M. Whole genome analysis of linezolid resistance in Streptococcus pneumoniae reveals resistance and compensatory mutations. BMC Genomics 12, 512 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Gao, W. et al. Two novel point mutations in clinical Staphylococcus aureus reduce linezolid susceptibility and switch on the stringent response to promote persistent infection. PLoS Pathog. 6, e1000944 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Leclercq, R. Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications. Clin. Infect. Dis. 34, 482–492 (2002).
  Article CAS PubMed Google Scholar
• Unemo, M. et al. High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob. Agents Chemother. 56, 1273–1280 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Katayama, Y., Ito, T. & Hiramatsu, K. A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 44, 1549–1555 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Shore, A. C. et al. Detection of staphylococcal cassette chromosome mec type XI carrying highly divergent mecA, mecI, mecR1, blaZ, and ccr genes in human clinical isolates of clonal complex 130 methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 55, 3765–3773 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Garcia-Ãlvarez, L. et al. Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study. Lancet Infect. Dis. 11, 595–603 (2011). This paper reports the identification of a new allele that is undetectable by conventional diagnostic tests.
  Article CAS PubMed PubMed Central Google Scholar
• Shore, A. C. & Coleman, D. C. Staphylococcal cassette chromosome mec: recent advances and new insights. Int. J. Med. Microbiol. 303, 350–359 (2013).
  Article CAS PubMed Google Scholar
• Stegger, M. et al. Rapid detection, differentiation and typing of methicillin-resistant Staphylococcus aureus harbouring either mecA or the new mecA homologue mecALGA251. Clin. Microbiol. Infect. 18, 395–400 (2012).
  Article CAS PubMed Google Scholar
• Cartwright, E. J. P. et al. Use of vitek 2 antimicrobial susceptibility profile to identify mecC in methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 51, 2732–2734 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Skov, R. et al. Phenotypic detection of _mecC_-MRSA: cefoxitin is more reliable than oxacillin. J. Antimicrob. Chemother. 69, 133–135 (2014).
  Article CAS PubMed Google Scholar
• Long, K. S., Poehlsgaard, J., Kehrenberg, C., Schwarz, S. & Vester, B. The Cfr rRNA methyltransferase confers resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A antibiotics. Antimicrob. Agents Chemother. 50, 2500–2505 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Shen, J., Wang, Y. & Schwarz, S. Presence and dissemination of the multiresistance gene cfr in Gram-positive and Gram-negative bacteria. J. Antimicrob. Chemother. 68, 1697–1706 (2013).
  Article CAS PubMed Google Scholar
• Zhang, W. J. et al. Characterization of the IncA/C plasmid pSCEC2 from Escherichia coli of swine origin that harbours the multiresistance gene cfr. J. Antimicrob. Chemother. 69, 385–389 (2014).
  Article CAS PubMed Google Scholar
• Fritsche, T. R., Castanheira, M., Miller, G. H., Jones, R. N. & Armstrong, E. S. Detection of methyltransferases conferring high-level resistance to aminoglycosides in Enterobacteriaceae from Europe, North America, and Latin America. Antimicrob. Agents Chemother. 52, 1843–1845 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Hidalgo, L. et al. Association of the novel aminoglycoside resistance determinant RmtF with NDM carbapenemase in Enterobacteriaceae isolated in India and the UK. J. Antimicrob. Chemother. 68, 1543–1550 (2013).
  Article CAS PubMed Google Scholar
• Vetting, M. W. et al. Structure of QnrB1, a plasmid-mediated fluoroquinolone resistance factor. J. Biol. Chem. 286, 25265–25273 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Cai, Y., Chai, D., Wang, R., Liang, B. & Bai, N. Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies. J. Antimicrob. Chemother. 67, 1607–1615 (2012).
  Article CAS PubMed Google Scholar
• Lim, L. M. et al. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy 30, 1279–1291 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Adams, M. D. et al. Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicrob. Agents Chemother. 53, 3628–3634 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Beceiro, A. et al. Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system. Antimicrob. Agents Chemother. 55, 3370–3379 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Fernandez, L. et al. Adaptive resistance to the “last hope” antibiotics polymyxin B and colistin in Pseudomonas aeruginosa is mediated by the novel two-component regulatory system ParR–ParS. Antimicrob. Agents Chemother. 54, 3372–3382 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Miller, A. K. et al. PhoQ mutations promote lipid A modification and polymyxin resistance of Pseudomonas aeruginosa found in colistin-treated cystic fibrosis patients. Antimicrob. Agents Chemother. 55, 5761–5769 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Cannatelli, A. et al. In vivo emergence of colistin resistance in Klebsiella pneumoniae producing KPC-type carbapenemases mediated by insertional inactivation of the PhoQ/PhoP mgrB regulator. Antimicrob. Agents Chemother. 57, 5521–5526 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Cannatelli, A. et al. MgrB inactivation is a common mechanism of colistin resistance in KPC carbapenemase-producing Klebsiella pneumoniae of clinical origin. Antimicrob. Agents Chemother. 58, 5696–5703 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Mishra, N. N. et al. Emergence of daptomycin resistance in daptomycin-naive rabbits with methicillin-resistant Staphylococcus aureus prosthetic joint infection is associated with resistance to host defense cationic peptides and mprF polymorphisms. PLoS ONE 8, e71151 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Davlieva, M., Zhang, W., Arias, C. A. & Shamoo, Y. Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci. Antimicrob. Agents Chemother. 57, 289–296 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Miller, C. et al. Adaptation of Enterococcus faecalis to daptomycin reveals an ordered progression to resistance. Antimicrob. Agents Chemother. 57, 5373–5383 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Diaz, L. et al. Whole-genome analyses of Enterococcus faecium isolates with diverse daptomycin MICs. Antimicrob. Agents Chemother. 58, 4527–4534 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Tran, T. T. et al. Daptomycin-resistant Enterococcus faecalis diverts the antibiotic molecule from the division septum and remodels cell membrane phospholipids. mBio 4, e00281-13 (2013). This study identifies a novel mode of daptomycin resistance in which redistribution of the target away from a key area of the cell results in resistance in enterococci.
  Article CAS PubMed PubMed Central Google Scholar
• Abraham, E. P. & Chain, E. An enzyme from bacteria able to destroy penicillin. 1940. Rev. Infect. Dis. 10, 677–678 (1988).
  Article CAS PubMed Google Scholar
• Livermore, D. M. Defining an extended-spectrum beta-lactamase. Clin. Microbiol. Infect. 14 (Suppl. 1), 3–10 (2008).
  Article CAS PubMed Google Scholar
• Nordmann, P., Poirel, L., Walsh, T. R. & Livermore, D. M. The emerging NDM carbapenemases. Trends Microbiol. 19, 588–595 (2011).
  Article CAS PubMed Google Scholar
• Voulgari, E., Poulou, A., Koumaki, V. & Tsakris, A. Carbapenemase-producing Enterobacteriaceae: now that the storm is finally here, how will timely detection help us fight back? Future Microbiol. 8, 27–39 (2013).
  Article CAS PubMed Google Scholar
• Woodford, N., Turton, J. F. & Livermore, D. M. Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance. FEMS Microbiol. Rev. 35, 736–755 (2011).
  Article CAS PubMed Google Scholar
• Johnson, A. P. & Woodford, N. Global spread of antibiotic resistance: the example of New Delhi metallo-β-lactamase (NDM)-mediated carbapenem resistance. J. Med. Microbiol. 62, 499–513 (2013).
  Article CAS PubMed Google Scholar
• Lynch, J. P., 3rd, Clark, N. M. & Zhanel, G. G. Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum β-lactamases and carbapenemases). Expert Opin. Pharmacother. 14, 199–210 (2013).
  Article CAS PubMed Google Scholar
• Rossolini, G. M., D'Andrea, M. M. & Mugnaioli, C. The spread of CTX-M-type extended-spectrum β-lactamases. Clin. Microbiol. Infect. 14 (Suppl. 1), 33–41 (2008).
  Article CAS PubMed Google Scholar
• Poirel, L., Bonnin, R. A. & Nordmann, P. Genetic support and diversity of acquired extended-spectrum β-lactamases in Gram-negative rods. Infect. Genet. Evol. 12, 883–893 (2012).
  Article CAS PubMed Google Scholar
• Zhao, W. H. & Hu, Z. Q. Epidemiology and genetics of CTX-M extended-spectrum β-lactamases in Gram-negative bacteria. Crit. Rev. Microbiol. 39, 79–101 (2013).
  Article CAS PubMed Google Scholar
• Dhanji, H. et al. Molecular epidemiology of fluoroquinolone-resistant ST131 Escherichia coli producing CTX-M extended-spectrum β-lactamases in nursing homes in Belfast, UK. J. Antimicrob. Chemother. 66, 297–303 (2011).
  Article CAS PubMed Google Scholar
• Cottell, J. L. et al. Complete sequence and molecular epidemiology of IncK epidemic plasmid encoding blaCTX-M-14. Emerg. Infect. Dis. 17, 645–652 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Cottell, J. L., Webber, M. A. & Piddock, L. J. Persistence of transferable extended-spectrum-β-lactamase resistance in the absence of antibiotic pressure. Antimicrob. Agents Chemother. 56, 4703–4706 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Dhanji, H. et al. Dissemination of pCT-like IncK plasmids harboring CTX-M-14 extended-spectrum β-lactamase among clinical Escherichia coli isolates in the United Kingdom. Antimicrob. Agents Chemother. 56, 3376–3377 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Queenan, A. M. & Bush, K. Carbapenemases: the versatile β-lactamases. Clin. Microbiol. Rev. 20, 440–458 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Queenan, A. M., Shang, W., Flamm, R. & Bush, K. Hydrolysis and inhibition profiles of β-lactamases from molecular classes A to D with doripenem, imipenem, and meropenem. Antimicrob. Agents Chemother. 54, 565–569 (2010).
  Article CAS PubMed Google Scholar
• Tzouvelekis, L. S., Markogiannakis, A., Psichogiou, M., Tassios, P. T. & Daikos, G. L. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clin. Microbiol. Rev. 25, 682–707 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Yigit, H. et al. Novel carbapenem-hydrolyzing β-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob. Agents Chemother. 45, 1151–1161 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Deshpande, L. M., Jones, R. N., Fritsche, T. R. & Sader, H. S. Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000–2004). Microb. Drug Resist. 12, 223–230 (2006).
  Article CAS PubMed Google Scholar
• Qi, Y. et al. ST11, the dominant clone of KPC-producing Klebsiella pneumoniae in China. J. Antimicrob. Chemother. 66, 307–312 (2011).
  Article CAS PubMed Google Scholar
• Leavitt, A., Chmelnitsky, I., Carmeli, Y. & Navon-Venezia, S. Complete nucleotide sequence of KPC-3-encoding plasmid pKpQIL in the epidemic Klebsiella pneumoniae sequence type 258. Antimicrob. Agents Chemother. 54, 4493–4496 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Woodford, N. et al. Outbreak of Klebsiella pneumoniae producing a new carbapenem-hydrolyzing class A β-lactamase, KPC-3, in a New York Medical Center. Antimicrob. Agents Chemother. 48, 4793–4799 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Woodford, N. et al. Arrival of Klebsiella pneumoniae producing KPC carbapenemase in the United Kingdom. J. Antimicrob. Chemother. 62, 1261–1264 (2008).
  Article CAS PubMed Google Scholar
• Kumarasamy, K. K. et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect. Dis. 10, 597–602 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Giske, C. G. et al. Diverse sequence types of Klebsiella pneumoniae contribute to the dissemination of _bla_NDM-1 in India, Sweden, and the United Kingdom. Antimicrob. Agents Chemother. 56, 2735–2738 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Kumarasamy, K. & Kalyanasundaram, A. Emergence of Klebsiella pneumoniae isolate co-producing NDM-1 with KPC-2 from India. J. Antimicrob. Chemother. 67, 243–244 (2012).
  Article CAS PubMed Google Scholar
• Walsh, T. R., Weeks, J., Livermore, D. M. & Toleman, M. A. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study. Lancet Infect. Dis. 11, 355–362 (2011).
  Article PubMed Google Scholar
• Nordmann, P., Poirel, L., Carrer, A., Toleman, M. A. & Walsh, T. R. How to detect NDM-1 producers. J. Clin. Microbiol. 49, 718–721 (2011).
  Article PubMed PubMed Central Google Scholar
• Shakil, S. et al. New Delhi metallo-β-lactamase (NDM-1): an update. J. Chemother. 23, 263–265 (2011).
  Article CAS PubMed Google Scholar
• Decousser, J. W. et al. Outbreak of NDM-1-producing Acinetobacter baumannii in France, January to May 2013. Euro Surveill. 18, 20547 (2013).
  Article PubMed Google Scholar
• Wright, G. D. Bacterial resistance to antibiotics: enzymatic degradation and modification. Adv. Drug Delivery Rev. 57, 1451–1470 (2005).
  Article CAS Google Scholar
• Norris, A. L. & Serpersu, E. H. Ligand promiscuity through the eyes of the aminoglycoside N3 acetyltransferase IIa. Protein Sci. 22, 916–928 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Romanowska, J., Reuter, N. & Trylska, J. Comparing aminoglycoside binding sites in bacterial ribosomal RNA and aminoglycoside modifying enzymes. Proteins 81, 63–80 (2013).
  Article CAS PubMed Google Scholar
• Qin, S. et al. Identification of a novel genomic island conferring resistance to multiple aminoglycoside antibiotics in Campylobacter coli. Antimicrob. Agents Chemother. 56, 5332–5339 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Spanogiannopoulos, P., Waglechner, N., Koteva, K. & Wright, G. D. A rifamycin inactivating phosphotransferase family shared by environmental and pathogenic bacteria. Proc. Natl Acad. Sci. USA 111, 7102–7107 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Bowser, T. E. et al. Novel anti-infection agents: small-molecule inhibitors of bacterial transcription factors. Bioorgan Med. Chem. Lett. 17, 5652–5655 (2007).
  Article CAS Google Scholar
• Bhullar, K. et al. Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS ONE 7, e34953 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• D'Costa, V. M. et al. Antibiotic resistance is ancient. Nature 477, 457–461 (2011).
  Article CAS PubMed Google Scholar
• Hernandez, J. et al. Human-associated extended-spectrum β-lactamase in the Antarctic. Appl. Environ. Microbiol. 78, 2056–2058 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Decousser, J. W., Poirel, L. & Nordmann, P. Characterization of a chromosomally encoded extended-spectrum class A β-lactamase from Kluyvera cryocrescens. Antimicrob. Agents Chemother. 45, 3595–3598 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Humeniuk, C. et al. β-lactamases of Kluyvera ascorbata, probable progenitors of some plasmid-encoded CTX-M types. Antimicrob. Agents Chemother. 46, 3045–3049 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Wellington, E. M. et al. The role of the natural environment in the emergence of antibiotic resistance in Gram-negative bacteria. Lancet Infect. Dis. 13, 155–165 (2013).
  Article CAS PubMed Google Scholar
• D'Costa, V. M. et al. Inactivation of the lipopeptide antibiotic daptomycin by hydrolytic mechanisms. Antimicrob. Agents Chemother. 56, 757–764 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Forsberg, K. J. et al. The shared antibiotic resistome of soil bacteria and human pathogens. Science 337, 1107–1111 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Perry, J. A. & Wright, G. D. The antibiotic resistance “mobilome”: searching for the link between environment and clinic. Front. Microbiol. 4, 138 (2013).
  Article PubMed PubMed Central Google Scholar