Chapter 69 : Mechanisms of Resistance to Antibacterial Agents*

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Mechanisms of Resistance to Antibacterial Agents*, Page 1 of 2

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This chapter describes mechanisms of antibiotic resistance in bacteria.

Citation: Patel J, Richter S. 2015. Mechanisms of Resistance to Antibacterial Agents*, p 1212-1245. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch69
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Serine β-lactamases and their reactions with β-lactam carbonyl donors. Modified from . doi:10.1128/9781555817381.ch69.f1

Citation: Patel J, Richter S. 2015. Mechanisms of Resistance to Antibacterial Agents*, p 1212-1245. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch69
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Image of FIGURE 2

Representation of the crystal structure of the AcrAB-TolC three-component RND multidrug efflux pump. On the left are the three components of the pumps as they link the cytoplasmic (inner) membrane to the outer membrane. The periplasmic linker protein (AcrA) is shown only in outline to allow visualization of the linkage between AcrB and TolC. On the right, an outline of the pump shown at the left is presented, detailing the functional regions of the pump. Reprinted with permission from . doi:10.1128/9781555817381.ch69.f2

Citation: Patel J, Richter S. 2015. Mechanisms of Resistance to Antibacterial Agents*, p 1212-1245. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch69
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Image of FIGURE 3

Sites of modification on kanamycin B by various AMEs. The arrows point to the sites of modification by the specific enzymes, namely, acetyltransferases, phosphotransferases, and nucleotidyltransferases. Reprinted with permission from . doi:10.1128/9781555817381.ch69.f3

Citation: Patel J, Richter S. 2015. Mechanisms of Resistance to Antibacterial Agents*, p 1212-1245. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch69
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1. Rice LB,, Yao JDC,, Klimm K,, Eliopoulos GM,, Moellering RC,Jr. 1991. Efficacy of different β-lactams against an extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain in the rat intra-abdominal abscess model. Antimicrob Agents Chemother 35:12431244.
2. Moellering RC,, Weinberg AN. 1971. Studies on antibiotic synergism against enterococci. II. Effect of various antibiotics on the uptake of 14C-labelled streptomycin by enterococci. J Clin Invest 50:25802584.
3. Rice LB,, Calderwood SB,, Eliopoulos GM,, Farber BF,, Karchmer AW. 1991. Enterococcal endocarditis: a comparison of native and prosthetic valve disease. Rev Infect Dis 13:17.
4. Roberts RB,, de Lancastre A,, Eisner W,, Severina EP,, Shopsin B,, Kreiswirth BN,, Tomasz A, the MRSA Collaborative Study Group. 1998. Molecular epidemiology of methicillin-resistant Staphylococcus aureus in 12 New York hospitals. J Infect Dis 178:164171.
5. Sherertz RJ,, Reagan DR,, Hampton KD,, Robertson KL,, Streed SA,, Hoen HM,, Thomas R,, Gwaltney JM,Jr. 1996. A cloud adult: the Staphylococcus aureus-virus interaction revisited. Ann Intern Med 124:539547.
6. Perl TM,, Cullen JJ,, Wenzel RP,, Zimmerman MB,, Pfaller MA,, Sheppard D,, Twombley J,, French P,, Herwaldt LA. 2002. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. J Engl J Med 346:18711877.
7. Adcock PM,, Pastor P,, Medley F,, Patterson JE,, Murphy TV. 1998. Methicillin-resistant Staphylococcus aureus in two child care centers. J Infect Dis 178:577580.
8. Wiener J,, Quinn JP,, Bradford PA,, Goering RV,, Nathan C,, Bush K,, Weinstein RA. 1999. Multiple antibiotic-resistant Klebsiella and Escherichia coli in nursing homes. JAMA 281:517523.
9. Ferber D. 2000. Antibiotic resistance. Superbugs on the hoof? Science 288:792794.
10. Ena J,, Lopez-Perezagua MM,, Martinez-Peinado C,, Cia-Barrio MA,, Ruiz-Lopez I. 1998. Emergence of ciprofloxacin resistance in Escherichia coli isolates after widespread use of fluoroquinolones. Diagn Microbiol Infect Dis 30:103107.
11. Wegener HC,, Aarestrup FM,, Jensen LB,, Hammerum AM,, Bager F. 1999. Use of antimicrobial growth promoters in food animals and Enterococcus faecium resistance to therapeutic antimicrobial drugs in Europe. Emerg Infect Dis 5:329335.
12. Marshall BM,, Levy SB. 2011. Food animals and antimicrobials: impacts on human health. Clin Microbiol Rev 24:718733.
13. Eliopoulos GM,, Farber BF,, Murray BE,, Wennersten C,, Moellering R,Jr. 1984. Ribosomal resistance of clinical enterococcal isolates to streptomycin. Antimicrob Agents Chemother 25:398399.
14. Martinez JL,, Alonso A,, Gomez-Gomez JM,, Baquero F. 1998. Quinolone resistance by mutations in chromosomal gyrase genes. Just the tip of the iceberg? J Antimicrob Chemother 42:683688.
15. Prystowsky J,, Siddiqui F,, Chosay J,, Shinabarger DL,, Millichap J,, Peterson LR,, Noskin GA. 2001. Resistance to linezolid: characterization of mutations in rRNA and comparison of their occurrences in vancomycin-resistant enterococci. Antimicrob Agents Chemother 45:21542156.
16. Jacobs C,, Frere JM,, Normark S. 1997. Cytosolic intermediates for cell wall biosynthesis and degradation control inducible β-lactam resistance in Gram-negative bacteria. Cell 88:823832.
17. Livermore DM. 1992. Interplay of impermeability and chromosomal β-lactamase activity in imipenem-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 36:20462048.
18. Podglajen I,, Breuil J,, Rohaut A,, Monsempes C,, Collatz E. 2001. Multiple mobile promoter regions for the rare carbapenem resistance gene of Bacteroides fragilis. J Bacteriol 183:35313535.
19. Sieradzki K,, Roberts RB,, Haber SW,, Tomasz A. 1999. The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection. J Engl J Med 340:517523.
20. Bjorkman J,, Nagaev I,, Berg OG,, Hughes D,, Andersson DI. 2000. Effects of environment on compensatory mutations to ameliorate costs of antibiotic resistance. Science 287:14791482.
21. Rice LB,, Carias LL,, Hutton-Thomas R,, Sifaoui F,, Gutmann L,, Rudin SD. 2001. Penicillin-binding protein 5 and expression of ampicillin resistance in Enterococcus faecium. Antimicrob Agents Chemother 45:14801486.
22. Murakami K,, Tomasz A. 1989. Involvement of multiple genetic determinants in high-level methicillin resistance in Staphylococcus aureus. J Bacteriol 171:874879.
23. D’Costa VM,, McGrann KM,, Hughes DW,, Wright GD. 2006. Sampling the antibiotic resistome. Science 311:374377.
24. Hakenbeck R,, Coyette J. 1998. Resistant penicillin-binding proteins. Cell Mol Life Sci 54:332340.
25. de la Campa AG,, Balsalobre L,, Ardanuy C,, Fenoll A,, Perez-Trallero E,, Linares J. 2004. Fluoroquinolone resistance in penicillin-resistant Streptococcus pneumoniae clones, Spain. Emerg Infect Dis 10:17511759.
26. Bruand C,, Chatelier L,, Ehrlich SD,, Janniere L. 1993. A fourth class of theta-replicating plasmids: the pAMβ1 family from Gram-positive bacteria. Proc Natl Acad Sci USA 90:1166811672.
27. Flannagan SE,, Chow JW,, Donabedian SM,, Brown WJ,, Perri MB,, Zervos MJ,, Ozawa Y,, Clewell DB. 2003. Plasmid content of a vancomycin-resistant Enterococcus faecalis isolate from a patient also colonized by Staphylococcus aureus with a VanA phenotype. Antimicrob Agents Chemother 47:39543959.
28. Weigel LM,, Clewell DB,, Gill SR,, Clark NC,, McDougal LK,, Flannagan SE,, Kolonay JF,, Shetty J,, Killgore GE,, Tenover FC. 2003. Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus. Science 302:15691571.
29. Ferretti JJ,, McShan WM,, Ajdic D,, Savic DJ,, Savic G,, Lyon K,, Primeaux C,, Sezate S,, Suvorov AN,, Kenton S,, Lai HS,, Lin SP,, Qian Y,, Jia HG,, Najar FZ,, Ren Q,, Zhu H,, Song L,, White J,, Yuan X,, Clifton SW,, Roe BA,, McLaughlin R. 2001. Complete genome sequence of an M1 strain of Streptococcus pyogenes. Proc Natl Acad Sci USA 98:46584663.
30. Rice LB. 2000. Bacterial monopolists: the bundling and dissemination of antimicrobial resistance genes in gram-positive bacteria. Clin Infect Dis 31:762769.
31. Rice LB. 1998. Tn916 family conjugative transposons and dissemination of antimicrobial resistance determinants. Antimicrob Agents Chemother 42:18711877.
32. Torres OR,, Korman RZ,, Zahler SA,, Dunny GM. 1991. The conjugative transposon Tn925: enhancement of conjugal transfer by tetracycline in Enterococcus faecalis and mobilization of chromosomal genes in both Bacillus subtilis and E. faecalis. Mol Gen Genet 225:395400.
33. Carias LL,, Rudin SD,, Donskey CJ,, Rice LB. 1998. Genetic linkage and cotransfer of a novel, vanB-containing transposon (Tn5382) and a low-affinity penicillin-binding protein 5 gene in a clinical vancomycin-resistant Enterococcus faecium isolate. J Bacteriol 180:44264434.
34. Arthur M,, Molinas C,, Depardieu F,, Courvalin P. 1993. Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J Bacteriol 175:117127.
35. Shaw JH,, Clewell DB. 1985. Complete nucleotide sequence of macrolide-lincosamide-streptogramin B resistance transposon Tn917 in Streptococcus faecalis. J Bacteriol 164:782796.
36. Galas DJ,, Chandler M,. 1989. Bacterial insertion sequences, p 109162. In Berg DE,, Howe MM (ed), Mobile DNA. American Society for Microbiology, Washington, DC.
37. Toleman MA,, Bennett PM,, Walsh TR. 2006. ISCR elements: novel gene-capturing systems of the 21st century? Microbiol Mol Biol Rev 70:296316.
38. Evers S,, Sahm DF,, Courvalin P. 1993. The vanB gene of vancomycin-resistant Enterococcus faecalis V583 is structurally-related to genes encoding D-ala:D-ala ligases and glycopeptide-resistance proteins VanA and VanC. Gene 124: 143144.
39. Hayashi T,, Makino K,, Ohnishi M,, Kurokawa K,, Ishii K,, Yokoyama K,, Han CG,, Ohtsubo E,, Nakayama K,, Murata T,, Tanaka M,, Tobe T,, Iida T,, Takami H,, Honda T,, Sasakawa C,, Ogasawara N,, Yasunaga T,, Kuhara S,, Shiba T,, Hattori M,, Shinagawa H. 2001. Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res 8:1122.
40. Welch RA,, Burland V,, Plunkett G,III,, Redford P,, Roesch P,, Rasko D,, Buckles EL,, Liou SR,, Boutin A,, Hackett J,, Stroud D,, Mayhew GF,, Rose DJ,, Zhou S,, Schwartz DC,, Perna NT,, Mobley HL,, Donnenberg MS,, Blattner FR. 2002. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci USA 99:1702017024.
41. Fitzgerald JR,, Sturdevant DE,, Mackie SM,, Gill SR,, Musser JM. 2001. Evolutionary genomics of Staphylococcus aureus: insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic. Proc Natl Acad Sci USA 98:88218826.
42. Paulsen IT,, Banerjei L,, Myers GS,, Nelson KE,, Seshadri R,, Read TD,, Fouts DE,, Eisen JA,, Gill SR,, Heidelberg JF,, Tettelin H,, Dodson RJ,, Umayam L,, Brinkac L,, Beanan M,, Daugherty S,, DeBoy RT,, Durkin S,, Kolonay J,, Madupu R,, Nelson W,, Vamathevan J,, Tran B,, Upton J,, Hansen T,, Shetty J,, Khouri H,, Utterback T,, Radune D,, Ketchum KA,, Dougherty BA,, Fraser CM. 2003. Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis. Science 299:20712074.
43. Jacoby GA,, Medeiros AA. 1991. More extended-spectrum β-lactamases. Antimicrob Agents Chemother 35:16971704.
44. Rice LB,, Carias LL,, Hujer AM,, Bonafede M,, Hutton R,, Hoyen C,, Bonomo RA. 2000. High-level expression of chromosomally encoded SHV-1 β-lactamase and an outer membrane protein change confer resistance to ceftazidime and piperacillin-tazobactam in a clinical isolate of Klebsiella pneumoniae. Antimicrob Agents Chemother 44:362367.
45. Jacobs C,, Joris B,, Jamin M,, Klarsov K,, Van Beeumen J,, Mengin-Lecreuix D,, van Heijenoort J,, Park JT,, Normark S,, Frère J-M. 1995. AmpD, essential for both β-lactamase regulation and cell wall recycling, is a novel cytosolic N-acetylmuramyl-L-alanine amidase. Mol Microbiol 15:553559.
46. Rather PN,, Orosz E,, Shaw KJ,, Hare R,, Miller G. 1993. Characterization and transcriptional regulation of the 2′-N-acetyltransferase gene from Providencia stuartii. J Bacteriol 175:64926498.
47. Shaw KJ,, Rather P,, Sabatelli F,, Mann P,, Munayyer H,, Mierzwa R,, Petrikkos G,, Hare RS,, Miller GH,, Bennett P,, Downey P. 1992. Characterization of the chromosomal aac(6′)-Ic gene from Serratia marcescens. Antimicrob Agents Chemother 36:14471455.
48. Weisblum B. 1995. Erythromycin resistance by ribosome modification. Antimicrob Agents Chemother 39:577585.
49. Arthur M,, Reynolds P,, Courvalin P. 1996. Glycopeptide resistance in enterococci. Trends Microbiol 4:401407.
50. Lee EH,, Nicolas MH,, Kitzis MD,, Pialoux G,, Collatz E,, Gutmann L. 1991. Association of two resistance mechanisms in a clinical isolate of Enterobacter cloacae with high-level resistance to imipenem. Antimicrob Agents Chemother 35:10931098.
51. Martinez-Martinez L,, Hernandez-Alles S,, Alberti S,, Tomas JM,, Benedi VJ,, Jacoby GA. 1996. In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum cephalosporins. Antimicrob Agents Chemother 40:342348.
52. Leclerq R,, Dutka-Malen S,, Brisson-Noel A,, Molinas C,, Derlot E,, Arthur M,, Duval J,, Courvalin P. 1992. Resistance of enterococci to aminoglycosides and glycopeptides. Clin Infect Dis 15:495501.
53. Murakami S,, Nakashima R,, Yamashita E,, Yamaguchi A. 2002. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 419:587593.
54. Lee A,, Mao W,, Warren MS,, Mistry A,, Hoshino K,, Okumura R,, Ishida H,, Lomovskaya O. 2000. Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance. J Bacteriol 182:31423150.
55. Mingeot-Leclercq MP,, Glupczynski Y,, Tulkens PM. 1999. Aminoglycosides: activity and resistance. Antimicrob Agents Chemother 43:727737.
56. Carter AP,, Clemons WM,, Brodersen DE,, Morgan-Warren RJ,, Wimberly BT,, Ramakrishnan V. 2000. Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature 407:340348.
57. Kadurugamuwa JL,, Lam JS,, Beveridge TJ. 1993. Interaction of gentamicin with the A band and B band lipopolysaccharides of Pseudomonas aeruginosa and its possible lethal effect. Antimicrob Agents Chemother 37:715721.
58. Campbell BD,, Kadner RJ. 1980. Relation of aerobiosis and ionic strength to the uptake of dihydrostreptomycin in Escherichia coli. Biochim Biophys Acta 593:110.
59. Jeannot K,, Sobel ML,, El Garch F,, Poole K,, Plesiat P. 2005. Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug-ribosome interaction. J Bacteriol 187:53415346.
60. Mao W,, Warren MS,, Lee A,, Mistry A,, Lomovskaya O. 2001. MexXY-OprM efflux pump is required for antagonism of aminoglycosides by divalent cations in Pseudomonas aeruginosa. Antimicrob Agents Chemother 45:20012007.
61. Aires JR,, Nikaido H. 2005. Aminoglycosides are captured from both periplasm and cytoplasm by the AcrD multidrug efflux transporter of Escherichia coli. J Bacteriol 187:19231929.
62. Manges AR,, Johnson JR,, Foxman B,, O’Bryan TT,, Fullerton KE,, Riley LW. 2001. Widespread distribution of urinary tract infections caused by a multidrug-resistant Escherichia coli clonal group. J Engl J Med 345:10071013.
63. Marchand I,, Damier-Piolle L,, Courvalin P,, Lambert T. 2004. Expression of the RND-type efflux pump AdeABC in Acinetobacter baumannii is regulated by the AdeRS two-component system. Antimicrob Agents Chemother 48:32983304.
64. Vakulenko SB,, Mobashery S. 2003. Versatility of aminoglycosides and prospects for their future. Clin Microbiol Rev 16:430450.
65. Maus CE,, Plikaytis BB,, Shinnick TM. 2005. Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother 49:31923197.
66. Galimand M,, Courvalin P,, Lambert T. 2003. Plasmid-mediated high-level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation. Antimicrob Agents Chemother 47:25652571.
67. Galimand M,, Sabtcheva S,, Courvalin P,, Lambert T. 2005. Worldwide disseminated armA aminoglycoside resistance methylase gene is borne by composite transposon Tn1548. Antimicrob Agents Chemother 49:29492953.
68. Yamane K,, Wachino J,, Doi Y,, Kurokawa H,, Arakawa Y. 2005. Global spread of multiple aminoglycoside resistance genes. Emerg Infect Dis 11:951953.
69. Yang J,, Ye L,, Wang W,, Luo Y,, Zhang Y,, Han L. 2011. Diverse prevalence of 16S rRNA methylase genes armA and rmtB amongst clinical multidrug-resistant Escherichia coli and Klebsiella pneumoniae isolates. Int J Antimicrob Agents 38:348351.
70. Galimand M,, Courvalin P,, Lambert T. 2012. RmtF, a new member of the aminoglycoside resistance 16S rRNA N7 G1405 methyltransferase family. Antimicrob Agents Chemother 56:39603962.
71. Bueno MF,, Francisco GR,, O’Hara JA,, de Oliveira Garcia D,, Doi Y. 2013. Coproduction of 16S rRNA methyltransferase RmtD or RmtG with KPC-2 and CTX-M group extended-spectrum beta-lactamases in Klebsiella pneumoniae. Antimicrob Agents Chemother 57:23972400.
72. Livermore DM,, Mushtaq S,, Warner M,, Zhang JC,, Maharjan S,, Doumith M,, Woodford N. 2011. Activity of aminoglycosides, including ACHN-490, against carbapenemresistant Enterobacteriaceae isolates. J Antimicrob Chemother 66:4853.
73. Azucena E,, Mobashery S. 2001. Aminoglycoside-modifying enzymes: mechanisms of catalytic processes and inhibition. Drug Resist Updates 4:106117.
74. Rather PN. 1998. Origins of aminoglycoside modifying enzymes. Drug Resist Updat 1:285291.
75. Shaw KJ,, Rather PN,, Hare RS,, Miller GH. 1993. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev 57:138163.
76. White PA,, McIver CJ,, Rawlinson WD. 2001. Integrons and gene cassettes in the Enterobacteriaceae. Antimicrob Agents Chemother 45:26582661.
77. Ferretti JJ,, Gilmore KS,, Courvalin P. 1986. Nucleotide sequence of the gene specifying the bifunctional 6′-aminoglycoside acetyltransferase-2″ aminoglycoside phosphotransferase enzyme in Streptococcus faecalis and identification and cloning of the gene regions specifying the two activities. J Bacteriol 167:631638.
78. Williamson R,, LaBouguenec C,, Gutmann L,, Horaud T. 1985. One or two low affinity penicillin-binding proteins may be responsible for the range of susceptibility of Enterococcus faecium to penicillin. J Gen Microbiol 131:19331940.
79. Tomasz A,. 1983. Murein hydrolases: enzymes in search of a physiologic function, p 155172. In Hackenbeck R,, Holtje J,, Labischinski H (ed), The Target of Penicillin. Walter de Gruyter, Berlin, Germany.
80. Henze UU,, Berger-Bachi B. 1995. Staphylococcus aureus penicillin-binding protein 4 and intrinsic β-lactam resistance. Antimicrob Agents Chemother 39:24152422.
81. Fontana R,, Aldegheri M,, Ligozzi M,, Lopez H,, Sucari A,, Satta G. 1994. Overproduction of a low-affinity penicillin-binding protein and high-level ampicillin resistance in Enterococcus faecium. Antimicrob Agents Chemother 38:19801983.
82. Chambers HF. 1997. Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications. Clin Microbiol Rev 10:781791.
83. Kosowska-Shick K,, McGhee PL,, Appelbaum PC. 2010. Affinity of ceftaroline and other β-lactams for penicillin-binding proteins from Staphylococcus aureus and Streptococcus pneumoniae. Antimicrob Agents Chemother 54:16701677.
84. Pinho MG,, de Lencastre H,, Tomasz A. 2001. An acquired and a native penicillin-binding protein cooperate in building the cell wall of drug-resistant staphylococci. Proc Natl Acad Sci USA 98:1088610891.
85. Arbeloa A,, Segal H,, Hugonnet JE,, Josseaume N,, Dubost L,, Brouard JP,, Gutmann L,, Mengin-Lecreulx D,, Arthur M. 2004. Role of class A penicillin-binding proteins in PBP5-mediated β-lactam resistance in Enterococcus faecalis. J Bacteriol 186:12211228.
86. Rice LB,, Carias LL,, Rudin S,, Hutton R,, Marshall S,, Hassan M,, Josseaume N,, Dubost L,, Marie A,, Arthur M. 2009. Role of class A penicillin-binding proteins in the expression of β-lactam resistance in Enterococcus faecium. J Bacteriol 191:36493656.
87. Couto I,, de Lencastre H,, Severina E,, Kloos W,, Webster JA,, Hubner RJ,, Sanches IS,, Tomasz A. 1996. Ubiquitous presence of a mecA homologue in natural isolates of Staphylococcus sciuri. Microb Drug Resist 2:377391.
88. Wu SW,, de Lencastre H,, Tomasz A. 2001. Recruitment of the mecA gene homologue of Staphylococcus sciuri into a resistance determinant and expression of the resistant phenotype in Staphylococcus aureus. J Bacteriol 183:24172424.
89. Hackbarth CJ,, Chambers HF. 1993. blaI and blaR1 regulate β-lactamase and PBP 2a production in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 37:11441149.
90. Arbeloa A,, Hugonnet JE,, Sentilhes AC,, Josseaume N,, Dubost L,, Monsempes C,, Blanot D,, Brouard JP,, Arthur M. 2004. Synthesis of mosaic peptidoglycan cross-bridges by hybrid peptidoglycan assembly pathways in gram-positive bacteria. J Biol Chem 279:4154641556.
91. Ito T,, Katayama Y,, Asada K,, Mori N,, Tsutsumimoto K,, Tiensasitorn C,, Hiramatsu K. 2001. Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 45:13231336.
92. Deurenberg RH,, Stobberingh EE. 2008. The evolution of Staphylococcus aureus. Infect Genet Evol 8:747763.
93. Zhang K,, McClure JA,, Elsayed S,, Conly JM. 2009. Novel staphylococcal cassette chromosome mec type, tentatively designated type VIII, harboring class A mec and type 4 ccr gene complexes in a Canadian epidemic strain of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 53:531540.
94. International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements (IWG-SCC). 2009. Classification of staphylococcal cassette chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements. Antimicrob Agents Chemother 53:49614967.
95. Fey PD,, Said-Salim B,, Rupp ME,, Hinrichs SH,, Boxrud DJ,, Davis CC,, Kreiswirth BN,, Schlievert PM. 2003. Comparative molecular analysis of community- or hospital-acquired methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 47:196203.
96. Katayama Y,, Robinson DA,, Enright MC,, Chambers HF. 2005. Genetic background affects stability of mecA in Staphylococcus aureus. J Clin Microbiol 43:23802383.
97. Paterson GK,, Harrison EM,, Holmes MA. 2014. The emergence of mecC methicillin-resistant Staphylococcus aureus. Trends Microbiol 22:4247
98. Barcus VA,, Ghanekar K,, Yeo M,, Coffey TJ,, Dowson CG. 1995. Genetics of high level penicillin resistance in clinical isolates of Streptococcus pneumoniae. FEMS Microbiol Lett 126:299303.
99. Smith AM,, Botha RF,, Koornhof HJ,, Klugman KP. 2001. Emergence of a pneumococcal clone with cephalosporin resistance and penicillin susceptibility. Antimicrob Agents Chemother 45:26482650.
100. Weber B,, Ehlert K,, Diehl A,, Reichmann P,, Labischinski H,, Hakenbeck R. 2000. The fib locus in Streptococcus pneumoniae is required for peptidoglycan crosslinking and PBP-mediated beta-lactam resistance. FEMS Microbiol Lett 188:8185.
101. Filipe SR,, Tomasz A. 2000. Inhibition of the expression of penicillin resistance in Streptococcus pneumoniae by inactivation of cell wall muropeptide branching genes. Proc Natl Acad Sci USA 97:48914896.
102. Spratt BG,, Zhang Q-Y,, Jones DM,, Hutchison A,, Brannigan JA,, Dowson CG. 1989. Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance in Neisseria meningitis disease. Proc Natl Acad Sci USA 86:89888992.
103. Sahm DF,, Marsilio MK,, Piazza G. 1999. Antimicrobial resistance in key bloodstream bacterial isolates: electronic surveillance with The Surveillance Network Database—USA. Clin Infect Dis 29:259263.
104. Donskey CJ,, Hanrahan JA,, Hutton RA,, Rice LB. 2000. Effect of parenteral antibiotic administration on establishment of colonization with vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract. J Infect Dis 181:18301833.
105. Rybkine T,, Mainardi JL,, Sougakoff W,, Collatz E,, Gutmann L. 1998. Penicillin-binding protein 5 sequence alterations in clinical isolates of Enterococcus faecium with different levels of β-lactam resistance. J Infect Dis 178:159163.
106. Rice LB,, Bellais S,, Carias LL,, Hutton-Thomas R,, Bonomo RA,, Caspers P,, Page MG,, Gutmann L. 2004. Impact of specific pbp5 mutations on expression of β-lactam resistance in Enterococcus faecium. Antimicrob Agents Chemother 48:30283032.
107. Dahesh S,, Hensler ME,, Van Sorge NM,, Gertz RE,, Schrag S,, Nizet V,, Beall BW. 2008. Point mutation in the group B streptococcal pbp2x gene conferring decreased susceptibility to β-lactam antibiotics. Antimicrob Agents Chemother 52:29152918.
108. Kimura K,, Suzuki S,, Wachino J,, Kurokawa H,, Yamane K,, Shibata N,, Nagano N,, Kato H,, Shibayama K,, Arakawa Y. 2008. First molecular characterization of group B streptococci with reduced penicillin susceptibility. Antimicrob Agents Chemother 52:28902897.
109. Longtin J,, Vermeiren C,, Shahinas D,, Tamber GS,, McGeer A,, Low DE,, Katz K,, Pillai DR. 2011. Novel mutations in a patient isolate of Streptococcus agalactiae with reduced penicillin susceptibility emerging after long-term oral suppressive therapy. Antimicrob Agents Chemother 55:29832985.
110. Hackbarth CJ,, Kocagoz T,, Kocagoz S,, Chambers HF. 1995. Point mutations in Staphylococcus aureus PBP 2 gene affect penicillin-binding kinetics and are associated with resistance. Antimicrob Agents Chemother 39:103106.
111. Mendes RE,, Tsakris A,, Sader HS,, Jones RN,, Biek D,, McGhee P,, Appelbaum PC,, Kosowska-Shick K. 2012. Characterization of methicillin-resistant Staphylococcus aureus displaying increased MICs of ceftaroline. J Antimicrob Chemother 67:13211324.
112. Ubukata K,, Shibasaki Y,, Yamamoto K,, Chiba N,, Hasegawa K,, Takeuchi Y,, Sunakawa K,, Inoue M,, Konno M. 2001. Association of amino acid substitutions in penicillin-binding protein 3 with β-lactam resistance in β-lactamase-negative ampicillin-resistant Haemophilus influenzae. Antimicrob Agents Chemother 45:16931699.
113. Bush K,, Jacoby GA. 2010. Updated functional classification of β-lactamases. Antimicrob Agents Chemother 54:969976.
114. Amoroso A,, Demares D,, Mollerach M,, Gutkind G,, Coyette J. 2001. All detectable high-molecular-mass penicillin-binding proteins are modified in a high-level β-lactam-resistant clinical isolate of Streptococcus mitis. Antimicrob Agents Chemother 45:20752081.
115. Bush K,, Jacoby GA,, Medeiros AA. 1995. A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 39:12111233.
116. Camargo IL,, Neoh HM,, Cui L,, Hiramatsu K. 2008. Serial daptomycin selection generates daptomycin-nonsusceptible Staphylococcus aureus strains with a heterogeneous vancomycin-intermediate phenotype. Antimicrob Agents Chemother 52:42894299.
117. Matagne A,, Lamotte-Brasseur J,, Frere JM. 1998. Catalytic properties of class A beta-lactamases: efficiency and diversity. Biochem J 330:581598.
118. Knox JR. 1995. Extended-spectrum and inhibitor-resistant TEM-type β-lactamases: mutations, specificity, and three-dimensional structure. Antimicrob Agents Chemother 39:25932601.
119. Nukaga M,, Mayama K,, Hujer AM,, Bonomo RA,, Knox JR. 2003. Ultrahigh resolution structure of a class A beta-lactamase: on the mechanism and specificity of the extended-spectrum SHV-2 enzyme. J Mol Biol 328:289301.
120. Meroueh SO,, Fisher JF,, Schlegel HB,, Mobashery S. 2005. Ab initio QM/MM study of class A beta-lactamase acylation: dual participation of Glu166 and Lys73 in a concerted base promotion of Ser70. J Am Chem Soc 127:1539715407.
121. Hall RM,, Collis CM. 1995. Mobile gene cassettes and integrons: capture and spread of genes by site-specific recombination. Mol Microbiol 15:593600.
122. Rowe-Magnus DA,, Guerout AM,, Mazel D. 2002. Bacterial resistance evolution by recruitment of super-integron gene cassettes. Mol Microbiol 43:16571669.
123. Stokes HW,, Hall RM. 1989. A novel family of potentially mobile DNA elements encoding site-specific gene integration function integrons. Mol Microbiol 3:16691683.
124. Weldhagen GF. 2004. Integrons and beta-lactamases—a novel perspective on resistance. Int J Antimicrob Agents 23:556562.
125. Navia MM,, Ruiz J,, Vila J. 2004. Molecular characterization of the integrons in Shigella strains isolated from patients with traveler’s diarrhea. Diagn Microbiol Infect Dis 48:175179.
126. Poirel L,, Gerome P,, De Champs C,, Stephanazzi J,, Naas T,, Nordmann P. 2002. Integron-located oxa-32 gene cassette encoding an extended-spectrum variant of OXA-2 β-lactamase from Pseudomonas aeruginosa. Antimicrob Agents Chemother 46:566569.
127. Poirel L,, Girlich D,, Naas T,, Nordmann P. 2001. OXA-28, an extended-spectrum variant of OXA-10 β-lactamase from Pseudomonas aeruginosa and its plasmid- and integron-located gene. Antimicrob Agents Chemother 45:447453.
128. Philippon A,, Labia R,, Jacoby GA. 1989. Extended-spectrum β-lactamases. Antimicrob Agents Chemother 33:11311136.
129. Ko WC,, Paterson DL,, Sagnimeni AJ,, Hansen DS,, Von Gottberg A,, Mohapatra S,, Casellas JM,, Goossens H,, Mulazimoglu L,, Trenholme G,, Klugman KP,, McCormack JG,, Yu VL. 2002. Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg Infect Dis 8:160166.
130. Livermore DM,, Brown DF,, Quinn JP,, Carmeli Y,, Paterson DL,, Yu VL. 2004. Should third-generation cephalosporins be avoided against AmpC-inducible Enterobacteriaceae? Clin Microbiol Infect 10:8485.
131. Castanheira M,, Toleman MA,, Jones RN,, Schmidt FJ,, Walsh TR. 2004. Molecular characterization of a β-lactamase gene, blaGIM-1, encoding a new subclass of metallo-beta-lactamase. Antimicrob Agents Chemother 48:46544661.
132. Paterson DL,, Ko WC,, Von Gottberg A,, Mohapatra S,, Casellas JM,, Goossens H,, Mulazimoglu L,, Trenholme G,, Klugman KP,, Bonomo RA,, Rice LB,, Wagener MM,, McCormack JG,, Yu VL. 2004. Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases. Clin Infect Dis 39:3137.
133. Paterson DL,, Ko WC,, Von A Gottberg,, Mohapatra S,, Casellas JM,, Goossens H,, Mulazimoglu L,, Trenholme G,, Klugman KP,, Bonomo RA,, Rice LB,, Wagener MM,, McCormack JG,, Yu VL. 2004. International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial infections. Ann Intern Med 140:2632.
134. Raquet X,, Lamotte-Brasseur J,, Fonze E,, Goussard S,, Courvalin P,, Frere JM. 1994. TEM beta-lactamase mutants hydrolysing third-generation cephalosporins. A kinetic and molecular modelling analysis. J Mol Biol 244:625639.
135. D’Andrea MM,, Arena F,, Pallecchi L,, Rossolini GM. 2013. CTX-M-type beta-lactamases: a successful story of antibiotic resistance. Int J Med Microbiol 303:305317.
136. Drawz SM,, Papp-Wallace KM,, Bonomo RA. 2014. New beta-lactamase inhibitors: a therapeutic renaissance in an MDR world. Antimicrob Agents Chemother 58:18351846.
137. Kim J,, Lim YM,, Jeong YS,, Seol SY. 2005. Occurrence of CTX-M-3, CTX-M-15, CTX-M-14, and CTX-M-9 extended-spectrum β-lactamases in Enterobacteriaceae clinical isolates in Korea. Antimicrob Agents Chemother 49:15721575.
138. Lartigue MF,, Poirel L,, Decousser JW,, Nordmann P. 2005. Multidrug-resistant Shigella sonnei and Salmonella enterica serotype Typhimurium isolates producing CTX-M beta-lactamases as causes of community-acquired infection in France. Clin Infect Dis 40:10691070.
139. Paterson DL,, Hujer KM,, Hujer AM,, Yeiser B,, Bonomo MD,, Rice LB,, Bonomo RA. 2003. Extended-spectrum β-lactamases in Klebsiella pneumoniae bloodstream isolates from seven countries: dominance and widespread prevalence of SHV- and CTX-M-type β-lactamases. Antimicrob Agents Chemother 47:35543560.
140. Bradford PA. 2001. Extended-spectrum β-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev 14:933951.
141. Bradford PA. 2001. What’s new in beta-lactamases? Curr Infect Dis Rep 3:1319.
142. Poirel L,, Naas T,, Guibert M,, Chaibi EB,, Labia R,, Nordmann P. 1999. Molecular and biochemical characterization of VEB-1, a novel class A extended-spectrum β-lactamase encoded by an Escherichia coli integron gene. Antimicrob Agents Chemother 43:573581.
143. Chen Y,, Delmas J,, Sirot J,, Shoichet B,, Bonnet R. 2005. Atomic resolution structures of CTX-M beta-lactamases: extended spectrum activities from increased mobility and decreased stability. J Mol Biol 348:349362.
144. Ibuka A,, Taguchi A,, Ishiguro M,, Fushinobu S,, Ishii Y,, Kamitori S,, Okuyama K,, Yamaguchi K,, Konno M,, Matsuzawa H. 1999. Crystal structure of the E166A mutant of extended-spectrum β-lactamase Toho-1 at 1.8 Å resolution. J Mol Biol 285:20792087.
145. Ibuka AS,, Ishii Y,, Galleni M,, Ishiguro M,, Yamaguchi K,, Frere JM,, Matsuzawa H,, Sakai H. 2003. Crystal structure of extended-spectrum beta-lactamase Toho-1: insights into the molecular mechanism for catalytic reaction and substrate specificity expansion. Biochemistry (Moscow) 42:1063410643.
146. Orencia MC,, Yoon JS,, Ness JE,, Stemmer WP,, Stevens RC. 2001. Predicting the emergence of antibiotic resistance by directed evolution and structural analysis. Nat Struct Biol 8:238242.
147. Shimamura T,, Ibuka A,, Fushinobu S,, Wakagi T,, Ishiguro M,, Ishii Y,, Matsuzawa H. 2002. Acyl-intermediate structures of the extended-spectrum class A beta-lactamase, Toho-1, in complex with cefotaxime, cephalothin, and benzylpenicillin. J Biol Chem 277:4660146608.
148. Tranier S,, Bouthors AT,, Maveyraud L,, Guillet V,, Sougakoff W,, Samama JP. 2000. The high resolution crystal structure for class A beta-lactamase PER-1 reveals the bases for its increase in breadth of activity. J Biol Chem 275:2807528082.
149. Wang X,, Minasov G,, Shoichet BK. 2002. Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs. J Mol Biol 320:8589.
150. Yigit H,, Queenan AM,, Anderson GJ,, Domenech-Sanchez A,, Biddle JW,, Steward CD,, Alberti S,, Bush K,, Tenover FC. 2001. Novel carbapenem-hydrolyzing β-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 45:11511161.
151. Nordmann P,, Mariotte S,, Naas T,, Labia R,, Nicolas MH. 1993. Biochemical properties of a carbapenemhydrolyzing β-lactamase from Enterobacter cloacae and cloning of the gene into Escherichia coli. Antimicrob Agents Chemother 37:939946.
152. Rasmussen BA,, Bush K,, Keeney D,, Yang Y,, Hare R,, O’Gara C,, Medeiros AA. 1996. Characterization of IMI-1 β-lactamase, a class A carbapenem-hydrolyzing enzyme from Enterobacter cloacae. Antimicrob Agents Chemother 40:20802086.
153. Naas T,, Nordmann P. 1994. Analysis of a carbapenem-hydrolyzing class A beta-lactamase from Enterobacter cloacae and of its LysR-type regulatory protein. Proc Natl Acad Sci USA 91:76937697.
154. Kaiser RM,, Castanheira M,, Jones RN,, Tenover F,, Lynfield R. 2013. Trends in Klebsiella pneumoniae carbapenemase-positive K. pneumoniae in US hospitals: report from the 2007–2009 SENTRY Antimicrobial Surveillance Program. Diag Microbiol Infect Dis 76:356360.
155. Woodford N,, Turton JF,, Livermore DM. 2011. Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance. FEMS Microbiol Rev 35:736755.
156. Nordmann P,, Poirel L. 2013. Strategies for identification of carbapenemase-producing Enterobacteriaceae. J Antimicrob Chemother 68:487489.
157. Clinical and Laboratory Standards Institute. 2014. Performance Standards for Antimicrobial Susceptibility Testing. Twenty-Fourth Informational Supplement. M100-S24. CLSI, Wayne, PA.
158. Vasoo S,, Cunningham SA,, Kohner PC,, Simner PJ,, Mandrekar JN,, Lolans K,, Hayden MK,, Patel R. 2013. Comparison of a novel, rapid chromogenic biochemical assay, the Carba NP test, with the modified Hodge test for detection of carbapenemase-producing Gram-negative bacilli. J Clin Microbiol 51:30973101.
159. Ke W,, Bethel CR,, Thomson JM,, Bonomo RA,, van den Akker F. 2007. Crystal structure of KPC-2: insights into carbapenemase activity in class A beta-lactamases. Biochemistry (Moscow) 46:57325740.
160. Queenan AM,, Bush K. 2007. Carbapenemases: the versatile β-lactamases. Clin Microbiol Rev 20:440458.
161. Poirel L,, Weldhagen GF,, Naas T,, De Champs C,, Dove MG,, Nordmann P. 2001. GES-2, a class A β-lactamase from Pseudomonas aeruginosa with increased hydrolysis of imipenem. Antimicrob Agents Chemother 45:25982603.
162. Frase H,, Shi Q,, Testero SA,, Mobashery S,, Vakulenko SB. 2009. Mechanistic basis for the emergence of catalytic competence against carbapenem antibiotics by the GES family of beta-lactamases. J Biol Chem 284:2950929513.
163. Bonomo RA,, Dawes CG,, Knox JR,, Shlaes DM. 1995. β-Lactamase mutations far from the active site influence inhibitor binding. Biochim Biophys Acta 1247:121125.
164. Delaire M,, Labia R,, Samama JP,, Masson JM. 1992. Site-directed mutagenesis at the active site of Escherichia coli TEM-1 beta-lactamase. Suicide inhibitor-resistant mutants reveal the role of arginine 244 and methionine 69 in catalysis. J Biol Chem 267:2060020606.
165. Farzaneh S,, Chaibi EB,, Peduzzi J,, Barthelemy M,, Labia R,, Blazquez J,, Baquero F. 1996. Implication of Ile-69 and Thr-182 residues in kinetic characteristics of IRT-3 (TEM-32) β-lactamase. Antimicrob Agents Chemother 40:24342436.
166. Prinarakis EE,, Miriagou V,, Tzelepi E,, Gazouli M,, Tzouvelekis LS. 1997. Emergence of an inhibitor-resistant beta-lactamase (SHV-10) derived from an SHV-5 variant. Antimicrob Agents Chemother 41:838840.
167. Saves I,, Burlet-Schiltz O,, Swaren P,, Lefevre F,, Masson JM,, Prome JC,, Samama JP. 1995. The asparagine to aspartic acid substitution at position 276 of TEM-35 and TEM-36 is involved in the beta-lactamase resistance to clavulanic acid. J Biol Chem 270:1824018245.
168. Swaren P,, Golemi D,, Cabantous S,, Bulychev A,, Maveyraud L,, Mobashery S,, Samama JP. 1999. X-ray structure of the Asn276Asp variant of the Escherichia coli TEM-1 beta-lactamase: direct observation of electrostatic modulation in resistance to inactivation by clavulanic acid. Biochemistry (Moscow) 38:95709576.
169. Thomson CJ,, Amyes SG. 1992. TRC-1: emergence of a clavulanic acid-resistant TEM beta-lactamase in a clinical strain. FEMS Microbiol Lett 70:113117.
170. Vakulenko SB,, Geryk B,, Kotra LP,, Mobashery S,, Lerner SA. 1998. Selection and characterization of β-lactam–β-lactamase inactivator-resistant mutants following PCR mutagenesis of the TEM-1 β-lactamase gene. Antimicrob Agents Chemother 42:15421548.
171. Vedel G,, Bellaouaj A,, Gilly L,, Labia R,, Phillipon A,, Nevot P,, Paul G. 1992. Clinical isolates of Escherichia coli producing TRI β-lactamases: novel TEM enzymes conferring resistance to β-lactamase inhibitors. J Antimicrob Chemother 30:449462.
172. Dubois V,, Poirel L,, Arpin C,, Coulange L,, Bebear C,, Nordmann P,, Quentin C. 2004. SHV-49, a novel inhibitor-resistant β-lactamase in a clinical isolate of Klebsiella pneumoniae. Antimicrob Agents Chemother 48:44664469.
173. Kaye KS,, Gold HS,, Schwaber MJ,, Venkataraman L,, Qi Y,, De Girolami PC,, Samore MH,, Anderson G,, Rasheed JK,, Tenover FC. 2004. Variety of β-lactamases produced by amoxicillin-clavulanate-resistant Escherichia coli isolated in the northeastern United States. Antimicrob Agents Chemother 48:15201525.
174. Fiett J,, Palucha A,, Miaczynska B,, Stankiewicz M,, Przondo-Mordarska H,, Hryniewicz W,, Gniadkowski M. 2000. A novel complex mutant β-lactamase, TEM-68, identified in a Klebsiella pneumoniae isolate from an outbreak of extended-spectrum β-lactamase-producing klebsiellae. Antimicrob Agents Chemother 44:14991505.
175. Neuwirth C,, Madec S,, Siebor E,, Pechinot A,, Duez JM,, Pruneaux M,, Fouchereau-Peron M,, Kazmierczak A,, Labia R. 2001. TEM-89 β-lactamase produced by a Proteus mirabilis clinical isolate: new complex mutant (CMT 3) with mutations in both TEM-59 (IRT-17) and TEM-3. Antimicrob Agents Chemother 45:35913594.
176. Poirel L,, Mammeri H,, Nordmann P. 2004. TEM-121, a novel complex mutant of TEM-type β-lactamase from Enterobacter aerogenes. Antimicrob Agents Chemother 48: 45284531.
177. Sirot D,, Recule C,, Chaibi EB,, Bret L,, Croize J,, Chanal-Claris C,, Labia R,, Sirot J. 1997. A complex mutant of TEM-1 β-lactamase with mutations encountered in both IRT-4 and extended-spectrum TEM-15, produced by an Escherichia coli clinical isolate. Antimicrob Agents Chemother 41:13221325.
178. Walsh TR,, Toleman MA,, Poirel L,, Nordmann P. 2005. Metallo-β-lactamases: the quiet before the storm? Clin Microbiol Rev 18:306325.
179. Galleni M,, Lamotte-Brasseur J,, Rossolini GM,, Spencer J,, Dideberg O,, Frere JM. 2001. Standard numbering scheme for class B β-lactamases. Antimicrob Agents Chemother 45:660663.
180. Carfi A,, Pares S,, Duee E,, Galleni M,, Duez C,, Frere JM,, Dideberg O. 1995. The 3-D structure of a zinc metallo-β-lactamase from Bacillus cereus reveals a new type of protein fold. EMBO J 14:49144921.
181. Concha NO,, Janson CA,, Rowling P,, Pearson S,, Cheever CA,, Clarke BP,, Lewis C,, Galleni M,, Frere JM,, Payne DJ,, Bateson JH,, Abdel-Meguid SS. 2000. Crystal structure of the IMP-1 metallo β-lactamase from Pseudomonas aeruginosa and its complex with a mercaptocarboxylate inhibitor: binding determinants of a potent, broad-spectrum inhibitor. Biochemistry (Moscow) 39:42884298.
182. Spencer J,, Clarke AR,, Walsh TR. 2001. Novel mechanism of hydrolysis of therapeutic beta-lactams by Stenotrophomonas maltophilia L1 metallo-beta-lactamase. J Biol Chem 276:3363833644.
183. Ullah JH,, Walsh TR,, Taylor IA,, Emery DC,, Verma CS,, Gamblin SJ,, Spencer J. 1998. The crystal structure of the L1 metallo-β-lactamase from Stenotrophomonas maltophilia at 1.7 Å resolution. J Mol Biol 284:125136.
184. Crowder MW,, Spencer J,, Vila AJ. 2006. Metallo-beta-lactamases: novel weaponry for antibiotic resistance in bacteria. Acc Chem Res 39:721728.
185. Alksne LE,, Rasmussen BA. 1997. Expression of the AsbA1, OXA-12, and AsbM1 β-lactamases in Aeromonas jandaei AER 14 is coordinated by a two-component regulon. J Bacteriol 179:20062013.
186. Pogue JM,, Mann T,, Barber KE,, Kaye KS. 2013. Carbapenem-resistant Acinetobacter baumannii: epidemiology, surveillance and management. Expert Rev Anti Infect Ther 11:383393.
187. Rodriguez-Martinez JM,, Nordmann P,, Fortineau N,, Poirel L. 2010. VIM-19, a metallo-β-lactamase with increased carbapenemase activity from Escherichia coli and Klebsiella pneumoniae. Antimicrob Agents Chemother 54:471476.
188. Dorete L,, Poirel L,, Nordmann P. 2014. Worldwide dissemination of the NDM-type carbapenemases in gram-negative bacteria. Biomed Res Int 2014:112.
189. Garau G,, Bebrone C,, Anne C,, Galleni M,, Frere JM,, Dideberg O. 2005. A metallo-beta-lactamase enzyme in action: crystal structures of the monozinc carbapenemase CphA and its complex with biapenem. J Mol Biol 345:785795.
190. Jacoby GA. 2009. AmpC β-lactamases. Clin Microbiol Rev 22:161182.
191. Crichlow GV,, Kuzin AP,, Nukaga M,, Mayama K,, Sawai T,, Knox JR. 1999. Structure of the extended-spectrum class C beta-lactamase of Enterobacter cloacae GC1, a natural mutant with a tandem tripeptide insertion. Biochemistry (Moscow) 38:1025610261.
192. Lobkovsky E,, Billings EM,, Moews PC,, Rahil J,, Pratt RF,, Knox JR. 1994. Crystallographic structure of a phosphonate derivative of the Enterobacter cloacae P99 cephalosporinase: mechanistic interpretation of a beta-lactamase transition-state analog. Biochemistry (Moscow) 33:67626772.
193. Minasov G,, Wang X,, Shoichet BK. 2002. An ultrahigh resolution structure of TEM-1 beta-lactamase suggests a role for Glu166 as the general base in acylation. J Am Chem Soc 124:53335340.
194. Chen Y,, Minasov G,, Roth TA,, Prati F,, Shoichet BK. 2006. The deacylation mechanism of AmpC beta-lactamase at ultrahigh resolution. J Am Chem Soc 128:29702976.
195. Gherman BF,, Goldberg SD,, Cornish VW,, Friesner RA. 2004. Mixed quantum mechanical/molecular mechanical (QM/MM) study of the deacylation reaction in a penicillin binding protein (PBP) versus in a class C beta-lactamase. J Am Chem Soc 126:76527664.
196. Brown NG,, Shanker S,, Venkataram Prasad BV,, Palzkill T. 2009. Structural and biochemical evidence that a TEM-1 β-lactamase N170G active site mutant acts via substrate-assisted catalysis. J Biol Chem 284:3370333712.
197. Chen Y,, McReynolds A,, Shoichet BK. 2009. Re-examining the role of Lys67 in class C beta-lactamase catalysis. Protein Sci 18:662669.
198. Oefner C,, D’Arcy A,, Daly JJ,, Gubernator K,, Charnas RL,, Heinze I,, Hubschwerlen C,, Winkler FK. 1990. Refined crystal structure of beta-lactamase from Citrobacter freundii indicates a mechanism for beta-lactam hydrolysis. Nature 343:284288.
199. Bradford PA,, Urban C,, Mariano N,, Projan SJ,, Rahal JJ,, Bush K. 1997. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC β-lactamase, and the loss of an outer membrane protein. Antimicrob Agents Chemother 41:563569.
200. Stapleton PD,, Shannon KP,, French GL. 1999. Carbapenem resistance in Escherichia coli associated with plasmid-determined CMY-4 β-lactamase production and loss of an outer membrane protein. Antimicrob Agents Chemother 43:12061210.
201. Naas T,, Nordmann P. 1999. OXA-type beta-lactamases. Curr Pharm Des 5:865879.
202. Poirel L,, Naas T,, Nordmann P. 2010. Diversity, epidemiology, and genetics of class D β-lactamases. Antimicrob Agents Chemother 54:2438.
203. Navia MM,, Ruiz J,, Vila J. 2002. Characterization of an integron carrying a new class D beta-lactamase (OXA-37) in Acinetobacter baumannii. Microb Drug Resist 8:261265.
204. Vila J,, Navia M,, Ruiz J,, Casals C. 1997. Cloning and nucleotide sequence analysis of a gene encoding an OXA-derived β-lactamase in Acinetobacter baumannii. Antimicrob Agents Chemother 41:27572759.
205. Maveyraud L,, Golemi D,, Kotra LP,, Tranier S,, Vakulenko S,, Mobashery S,, Samama JP. 2000. Insights into class D beta-lactamases are revealed by the crystal structure of the OXA10 enzyme from Pseudomonas aeruginosa. Struct Fold Des 8:12891298.
206. Paetzel M,, Danel F,, de Castro L,, Mosimann SC,, Page MG,, Strynadka NC. 2000. Crystal structure of the class D beta-lactamase OXA-10. Nat Struct Biol 7:918925.
207. Paton R,, Miles RS,, Hood J,, Amyes SGB. 1993. ARI-1: beta-lactamase-mediated imipenem resistance in Acinetobacter baumannii. Int J Antimicrob Agents 2:8188.
208. Heritier C,, Poirel L,, Lambert T,, Nordmann P. 2005. Contribution of acquired carbapenem-hydrolyzing oxacillinases to carbapenem resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 49:31983202.
209. Heritier C,, Poirel L,, Fournier PE,, Claverie JM,, Raoult D,, Nordmann P. 2005. Characterization of the naturally occurring oxacillinase of Acinetobacter baumannii. Antimicrob Agents Chemother 49:41744179.
210. Bou G,, Oliver A,, Martinez-Beltran J. 2000. OXA-24, a novel class D β-lactamase with carbapenemase activity in an Acinetobacter baumannii clinical strain. Antimicrob Agents Chemother 44:15561561.
211. Santillana E,, Beceiro A,, Bou G,, Romero A. 2007. Crystal structure of the carbapenemase OXA-24 reveals insights into the mechanism of carbapenem hydrolysis. Proc Natl Acad Sci USA 104:53545359.
212. Docquier JD,, Calderone V,, De Luca F,, Benvenuti M,, Giuliani F,, Bellucci L,, Tafi A,, Nordmann P,, Botta M,, Rossolini GM,, Mangani S. 2009. Crystal structure of the OXA-48 beta-lactamase reveals mechanistic diversity among class D carbapenemases. Chem Biol 16:540547.
213. Poirel L,, Potron A,, Nordmann P. 2012. OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother 67:15971606.
214. Murray IA,, Shaw WV. 1997. O-Acetyltransferases for chloramphenicol and other natural products. Antimicrob Agents Chemother 41:16.
215. Schwarz S,, Kehrenberg C,, Doublet B,, Cloeckaert A. 2004. Molecular basis of bacterial resistance to chloramphenicol and florfenicol. FEMS Microbiol Rev 28:519542.
216. Shaw WV. 1983. Chloramphenicol acetyltransferase: enzymology and molecular biology. CRC Crit Rev Biochem 14:146.
217. Fitton JE,, Shaw WV. 1979. Comparison of chloramphenicol acetyltransferase variants in staphylococci. Purification, inhibitor studies and N-terminal sequences. Biochem J 177:575582.
218. Murray IA,, Martinez-Suarez JV,, Close TJ,, Shaw WV. 1990. Nucleotide sequences of genes encoding the type II chloramphenicol acetyltransferases of Escherichia coli and Haemophilus influenzae, which are sensitive to inhibition by thiol-reactive reagents. Biochem J 272:505510.
219. Beaman TW,, Sugantino M,, Roderick SL. 1998. Structure of the hexapeptide xenobiotic acetyltransferase from Pseudomonas aeruginosa. Biochemistry (Moscow) 37:66896696.
220. Qiu W,, Shi R,, Lu ML,, Zhou M,, Roy PH,, Lapointe J,, Lin SX. 2004. Crystal structure of chloramphenicol acetyltransferase B2 encoded by the multiresistance transposon Tn2424. Proteins 57:858861.
221. Nikaido H. 1998. Multiple antibiotic resistance and efflux. Curr Opin Microbiol 1:516523.
222. Bissonnette L,, Champetier S,, Buisson JP,, Roy PH. 1991. Characterization of the nonenzymatic chloramphenicol resistance (cmlA) gene of the In4 integron of Tn1696: similarity of the product to transmembrane transport proteins. J Bacteriol 173:44934502.
223. Bolton LF,, Kelley LC,, Lee MD,, Fedorka-Cray PJ,, Maurer JJ. 1999. Detection of multidrug-resistant Salmonella enterica serotype Typhimurium DT104 based on a gene which confers cross-resistance to florfenicol and chloramphenicol. J Clin Microbiol 37:13481351.
224. White DG,, Hudson C,, Maurer JJ,, Ayers S,, Zhao S,, Lee MD,, Bolton L,, Foley T,, Sherwood J. 2000. Characterization of chloramphenicol and florfenicol resistance in Escherichia coli associated with bovine diarrhea. J Clin Microbiol 38:45934598.
225. Roca I,, Marti S,, Espinal P,, Martínez P,, Gibert I,, Vila J. 2009. CraA, a major facilitator superfamily efflux pump associated with chloramphenicol resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 53:40134014.
226. Fowler VG,Jr,, Boucher HW,, Corey GR,, Abrutyn E,, Karchmer AW,, Rupp ME,, Levine DP,, Chambers HF,, Tally FP,, Vigliani GA,, Cabell CH,, Link AS,, DeMeyer I,, Filler SG,, Zervos M,, Cook P,, Parsonnet J,, Bernstein JM,, Price CS,, Forrest GN,, Fatkenheuer G,, Gareca M,, Rehm SJ,, Brodt HR,, Tice A,, Cosgrove SE. 2006. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. J Engl J Med 355:653665.
227. Mishra NN,, Yang SJ,, Sawa A,, Rubio A,, Nast CC,, Yeaman MR,, Bayer AS. 2009. Analysis of cell membrane characteristics of in vitro-selected daptomycin-resistant strains of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 53:23122318.
228. Peleg AY,, Miyakis S,, Ward DV,, Earl AM,, Rubio A,, Cameron DR,, Pillai S,, Moellerng RC,Jr,, Eliopoulos GM. 2012. Whole genome characterization of the mechanisms of daptomycin resistance in clinical and laboratory derived isolates of Staphylococcus aureus. PLoS One 7:e28316. 10.1371/journal.pone.0028316.
229. Belcheva A,, Golemi-Kotra D. 2008. A close-up view of the VraSR two-component system. A mediator of Staphylococcus aureus response to cell wall damage. J Biol Chem 283:1235412364.
230. Mehta S,, Cuirolo AX,, Plata KB,, Silverman RS,, Rubio JA,, Rosato AE. 2012. VraSR two-component regulatory system contributes to mprF-mediated decreased susceptibility to daptomycin in in vivo-selected clinical strains of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 56:92102.
231. Camargo IL,, Neoh HM,, Cui L,, Hiramatsu K. 2008. Serial daptomycin selection generates daptomycin-nonsusceptible Staphylococcus aureus strains with a heterogeneous vancomycin-intermediate phenotype. Antimicrob Agents Chemother 52:42894299.
232. Cui L,, Iwamoto A,, Lian JQ,, Neoh HM,, Maruyama T,, Horikawa Y,, Hiramatsu K. 2006. Novel mechanism of antibiotic resistance originating in vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother 50:428438.
233. Humphries RM,, Pollett S,, Sakoulas G. 2013. A current perspective on daptomycin for the clinical microbiologist. Clin Microbiol Rev 26:759779.
234. Arias CA,, Panesso D,, McGrath DM,, Qin X,, Mojica MF,, Miller C,, Diaz L,, Tran TT,, Rincon S,, Barbu EM,, Reyes J,, Roh JH,, Sodergren LE,, Pasqualini R,, Arap W,, Quinn JP,, Shamoo Y,, Murray BE,, Weinstock GM. 2011. Genetic basis for in vivo daptomycin resistance in enterococci. N Engl J Med 365:892900.
235. Tran TT,, Panesso D,, Gao H,, Roh JH,, Munita JM,, Reyes J,, Diaz L,, Lobos EA,, Shamoo Y,, Mishra NN,, Bayer AS,, Murray BE,, Weinstock GM,, Arias CA. 2013. Whole genome sequencing of a daptomycin-susceptible Enterococcus faecium strain and its daptomycin-resistant variant arising during therapy. Antimicrob Agents Chemother 57:261268.
236. Lebreton F,, Depardieu F,, Bourdon N,, Fines-Guyon M,, Berger P,, Camiade S,, Leclercq R,, Courvalin P,, Cattoir V. 2011. D-Ala-D-Ser VanN-type transferable vancomycin resistance in Enterococcus faecium. Antimicrob Agents Chemother 55:46064612.
237. McKessar SJ,, Beryy AM,, Bell JM,, Turnidge JD,, Paton JC. 2000. Genetic charcterization of vanG, a novel vancomycin resistance locus of Enterococcus faecalis. Antimicrob Agents Chemother 44:32243228.
238. Xu X,, Lin D,, Yan G,, Ye X,, Wu S,, Guo Y,, Zhu D,, Hu F,, Zhang Y,, Wang F,, Jacoby GA,, Wang M. 2010. vanM, a new glycopeptide resistance gene cluster found in Enterococcus faecium. Antimicrob Agents Chemother 54:46434647.
239. Arthur M,, Depardieu F,, Molinas C,, Reynolds P,, Courvalin P. 1995. The vanZ gene of Tn1546 from Enterococcus faecium BM4147 confers resistance to teicoplanin. Gene 154:8792.
240. Arthur M,, Molinas C,, Courvalin P. 1992. The VanS-VanR two-component regulatory system controls synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium 4147. J Bacteriol 174:25822591.
241. Evers S,, Courvalin P. 1996. Regulation of VanB-type vancomycin resistance gene expression by the VanSB-VanRB two-component regulatory system in Enterococcus faecalis V583. J Bacteriol 178:13021309.
242. Hughes D. 2003. Exploiting genomics, genetics and chemistry to combat antibiotic resistance. Nat Rev Genet 4:432441.
243. Aslangul E,, Baptista M,, Fantin B,, Depardieu F,, Arthur M,, Courvalin P,, Carbon C. 1997. Selection of glycopeptide-resistant mutants of VanB-type Enterococcus faecalis BM4281 in vitro and in experimental endocarditis. J Infect Dis 175:598605.
244. Hayden MK,, Trenholm GM,, Schultz JE,, Sahm DF. 1993. In vivo development of teicoplanin resistance in a VanB Enterococcus faecium isolate. J Infect Dis 167:12241227.
245. Kaatz GW,, Seo SM,, Dorman NJ,, Lerner SA. 1990. Emergence of teicoplanin resistance during therapy of Staphylococcus aureus endocarditis. J Infect Dis 162:103108.
246. Darini AL,, Palepou MF,, Woodford N. 2000. Effects of the movement of insertion sequences on the structure of VanA glycopeptide resistance elements in Enterococcus faecium. Antimicrob Agents Chemother 44:13621364.
247. Garnier F,, Taourit S,, Glaser P,, Courvalin P,, Galimand M. 2000. Characterization of transposon Tn1549, conferring VanB-type resistance in Enterococcus spp. Microbiology 146:14811489.
248. Dahl KH,, Lundblad EW,, Rokenes TP,, Olsvik O,, Sundsfjord A. 2000. Genetic linkage of the vanB2 gene cluster to Tn5382 in vancomycin-resistant enterococci and characterization of two novel insertion sequences. Microbiology 146:14691479.
249. Leavis H,, Top J,, Shankar N,, Borgen K,, Bonten M,, van Embden J,, Willems RJ. 2004. A novel putative enterococcal pathogenicity island linked to the esp virulence gene of Enterococcus faecium and associated with epidemicity. J Bacteriol 186:672682.
250. Leavis HL,, Willems RJ,, van Wamel WJ,, Schuren FH,, Caspers MP,, Bonten MJ. 2007. Insertion sequence-driven diversification creates a globally dispersed emerging multiresistant subspecies of E. faecium. PLoS Pathog 3:e7. 10.1371/journal.ppat.0030007.
251. Noble WC,, Virani Z,, Gee RGA. 1992. Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett 93:195198.
252. Périchon B,, Courvalin P. 2009. VanA-type vancomycin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 53:45804587.
253. Limbago BM,, Kallen AJ,, Zhu W,, Eggers P,, McDougal LK,, Albrecht VS. 2014. Report of the 13th vancomycin resistant Staphylococcus aureus isolate from the United States. J Clin Microbiol 52:9981002.
254. Melo-Cristino J,, Resina C,, Manuel V,, Lito L,, Ramirez M. 2013. First case of infection with vancomycin resistant Staphylococus aureus in Europe. Lancet 382:205.
255. Dutka-Malen S,, Blaimont B,, Wauters G,, Courvalin P. 1994. Emergence of high-level resistance to glycopeptides in Enterococcus gallinarum and Enterococcus casseliflavus. Antimicrob Agents Chemother 38:16751677.
256. Vincent S,, Minkler P,, Bincziewski B,, Etter L,, Shlaes DM. 1992. Vancomycin resistance in Enterococcus gallinarum. Antimicrob Agents Chemother 36:13921399.
257. Fines M,, Perichon B,, Reynolds P,, Sahm DF,, Courvalin P. 1999. VanE, a new type of acquired glycopeptide resistance in Enterococcus faecalis BM4405. Antimicrob Agents Chemother 43:21612164.
258. Nichols M,, Schrag SJ. 2014. Two cases of invasive vancomycin-resistant group B streptococcus infection. N Engl J Med 370:885886.
259. Casadewall B,, Reynolds PE,, Courvalin P. 2001. Regulation of expression of the vanD glycopeptide resistance gene cluster from Enterococcus faecium BM4339. J Bacteriol 183:34363446.
260. Howden BP,, Davies JK,, Johnson PDR,, Stinear TP,, Grayson ML. 2010. Reduced vancomycin resistance in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin Microbiol Rev 23:99139.
261. Cui L,, Neoh H,, Shoji M,, Hiramatsu K. 2009. Contribution of vraSR and graSR point mutations to vancomycin resistance in vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother 53:12311234.
262. Belcheva A,, Golemi-Kotra D. 2008. A close-up view of the VraSR two-component system. A mediator of Staphylococcus aureus response to cell wall damage. J Biol Chem 283:1235412364.
263. Katayama Y,, Murakami H-Kuroda,, Cui L,, Hiramatsu K. 2009. Selection of heterogeneous vancomycin-intermediate Staphylococcus aureus by imipenem. Antimicrob Agents Chemother 53:31903196.
264. Climo MW,, Patron RL,, Archer GL. 1999. Combinations of vancomycin and β-lactams are synergistic against staphylococci with reduced susceptibilities to vancomycin. Antimicrob Agents Chemother 43:17471753.
265. Billot-Klein D,, Gutmann L,, Bryant D,, Bell D,, van Heijenoort J,, Grewal J,, Shlaes DM. 1996. Peptidoglycan synthesis and structure in Staphylococcus haemolyticus expressing increasing levels of resistance to glycopeptide antibiotics. J Bacteriol 178:46964703.
266. Levine DP,, Fromm BS,, Reddy BR. 1991. Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 115:674680.
267. Chang FY,, Peacock JE,Jr,, Musher DM,, Triplett P,, MacDonald BB,, Mylotte JM,, O’Donnell A,, Wagener MM,, Yu VL. 2003. Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore) 82: 333339.
268. Tuomanen E,, Tomasz A. 1990. Mechanism of phenotypic tolerance of nongrowing pneumococci to beta-lactam antibiotics. Scand J Infect Dis Suppl 74:102112.
269. Henriques Normark B,, Novak R,, Ortqvist A,, Kallenius G,, Tuomanen E,, Normark S. 2001. Clinical isolates of Streptococcus pneumoniae that exhibit tolerance of vancomycin. Clin Infect Dis 32:552558.
270. Haas W,, Sublett J,, Kaushal D,, Tuomanen EI. 2004. Revising the role of the pneumococcal vex-vncRS locus in vancomycin tolerance. J Bacteriol 186:84638471.
271. Shinabarger DL,, Marotti KR,, Murray RW,, Lin AH,, Melchior EP,, Swaney SM,, Dunyak DS,, Demyan WF,, Buysse JM. 1997. Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions. Antimicrob Agents Chemother 41:21322136.
272. Jones RN,, Ross JE,, Castanheira M,, Mendes RE. 2008. United States resistance surveillance results for linezolid (LEADER Program for 2007). Diagn Microbiol Infect Dis 62:416426.
273. Marshall SH,, Donskey CJ,, Hutton-Thomas R,, Salata RA,, Rice LB. 2002. Gene dosage and linezolid resistance in Enterococcus faecium and Enterococcus faecalis. Antimicrob Agents Chemother 46:33343336.
274. Wolter N,, Smith AM,, Farrell DJ,, Schaffner W,, Moore M,, Whitney CG,, Jorgensen JH,, Klugman KP. 2005. Novel mechanism of resistance to oxazolidinones, macrolides, and chloramphenicol in ribosomal protein L4 of the pneumococcus. Antimicrob Agents Chemother 49:35543557.
275. Lobritz M,, Hutton-Thomas R,, Marshall S,, Rice LB. 2003. Recombination proficiency influences frequency and locus of mutational resistance to linezolid in Enterococcus faecalis. Antimicrob Agents Chemother 47:33183320.
276. Arias CA,, Vallejo M,, Reyes J,, Panesso D,, Moreno J,, Castaneda E,, Villegas MV,, Murray BE,, Quinn JP. 2008. Clinical and microbiological aspects of linezolid resistance mediated by the cfr gene encoding a 23S rRNA methyltransferase. J Clin Microbiol 46:892896.
277. Weisblum B. 1995. Erythromycin resistance by ribosome modification. Antimicrob Agents Chemother 39:577585.
278. Zhong P,, Shortridge VD. 2000. The role of efflux in macrolide resistance. Drug Resist Updat 3:325329.
279. Douthwaite S,, Hansen LH,, Mauvais P. 2000. Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA. Mol Microbiol 36:183193.
280. Balfour JA,, Figgitt DP. 2001. Telithromycin. Drugs 61:815829.
281. Soltani M,, Beighton D,, Philpott-Howard J,, Woodford N. 2000. Mechanisms of resistance to quinupristin-dalfopristin among isolates of Enterococcus faecium from animals, raw meat, and hospital patients in Western Europe. Antimicrob Agents Chemother 44:433436.
282. Hayes JR,, Wagner DD,, English LL,, Carr LE,, Joseph SW. 2005. Distribution of streptogramin resistance determinants among Enterococcus faecium from a poultry production environment of the USA. J Antimicrob Chemother 55:123126.
283. van der Wouden EJ,, Thijs JC,, Kusters JG,, van Zwet AA,, Kleibeuker JH. 2001. Mechanism and clinical significance of metronidazole resistance in Helicobacter pylori. Scand J Gastroenterol Suppl 2001:1014.
284. Edwards DI. 1993. Nitroimidazole drugs—action and resistance mechanisms. II. Mechanisms of resistance. J Antimicrob Chemother 31:201210.
285. Edwards DI. 1993. Nitroimidazole drugs—action and resistance mechanisms. I. Mechanisms of action. J Antimicrob Chemother 31:920.
286. Carlier JP,, Sellier N,, Rager MN,, Reysset G. 1997. Metabolism of a 5-nitroimidazole in susceptible and resistant isogenic strains of Bacteroides fragilis. Antimicrob Agents Chemother 41:14951499.
287. Leiros HK,, Kozielski-Stuhrmann S,, Kapp U,, Terradot L,, Leonard GA,, McSweeney SM. 2004. Structural basis of 5-nitroimidazole antibiotic resistance: the crystal structure of NimA from Deinococcus radiodurans. J Biol Chem 279:5584055849.
288. Soki J,, Gal M,, Brazier JS,, Rotimi VO,, Urban E,, Nagy E,, Duerden BI. 2005. Molecular investigation of genetic elements contributing to metronidazole resistance in Bacteroides strains. J Antimicrob Chemother 57:212220.
289. Leitsch D,, Kolarich D,, Binder M,, Stadlmann J,, Altmann F,, Duchene M. 2009. Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance. Mol Microbiol 72:518536.
290. Guay DR. 2001. An update on the role of nitrofurans in the management of urinary tract infections. Drugs 61: 353364.
291. McOsker CC,, Fitzpatrick PM. 1994. Nitrofurantoin: mechanism of action and implications for resistance development in common uropathogens. J Antimicrob Chemother 33(Suppl A):2330.
292. Race PR,, Lovering AL,, Green RM,, Ossor A,, White SA,, Searle PF,, Wrighton CJ,, Hyde EI. 2005. Structural and mechanistic studies of Escherichia coli nitroreductase with the antibiotic nitrofurazone. Reversed binding orientations in different redox states of the enzyme. J Biol Chem 280:1325613264.
293. Sandegren L,, Lindqvist A,, Kahlmeter G,, Andersson DI. 2008. Nitrofurantoin resistance mechanism and fitness cost in Escherichia coli. J Antimicrob Chemother 62:495503.