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Mechanisms of Bacterial Resistance to Antimicrobial Agents

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  • Authors: Engeline van Duijkeren1, Anne-Kathrin Schink2, Marilyn C. Roberts3, Yang Wang4, Stefan Schwarz5
  • Editors: Frank Møller Aarestrup6, Stefan Schwarz7, Jianzhong Shen8, Lina Cavaco9
    Affiliations: 1: Center for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands; 2: Institute of Microbiology and Epizootics, Centre of Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany; 3: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195-7234; 4: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China; 5: Institute of Microbiology and Epizootics, Centre of Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany; 6: Technical University of Denmark, Lyngby, Denmark; 7: Freie Universität Berlin, Berlin, Germany; 8: China Agricultural University, Beijing, China; 9: Statens Serum Institute, Copenhagen, Denmark
  • Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0019-2017
  • Received 24 February 2017 Accepted 06 November 2017 Published 13 April 2018
  • Stefan Schwarz, [email protected]
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  • Abstract:

    During the past decades resistance to virtually all antimicrobial agents has been observed in bacteria of animal origin. This chapter describes in detail the mechanisms so far encountered for the various classes of antimicrobial agents. The main mechanisms include enzymatic inactivation by either disintegration or chemical modification of antimicrobial agents, reduced intracellular accumulation by either decreased influx or increased efflux of antimicrobial agents, and modifications at the cellular target sites (i.e., mutational changes, chemical modification, protection, or even replacement of the target sites). Often several mechanisms interact to enhance bacterial resistance to antimicrobial agents. This is a completely revised version of the corresponding chapter in the book published in 2006. New sections have been added for oxazolidinones, polypeptides, mupirocin, ansamycins, fosfomycin, fusidic acid, and streptomycins, and the chapters for the remaining classes of antimicrobial agents have been completely updated to cover the advances in knowledge gained since 2006.

  • Citation: van Duijkeren E, Schink A, Roberts M, Wang Y, Schwarz S. 2018. Mechanisms of Bacterial Resistance to Antimicrobial Agents. Microbiol Spectrum 6(2):ARBA-0019-2017. doi:10.1128/microbiolspec.ARBA-0019-2017.


1. Schwarz S, Chaslus-Dancla E. 2001. Use of antimicrobials in veterinary medicine and mechanisms of resistance. Vet Res 32:201–225 http://dx.doi.org/10.1051/vetres:2001120. [PubMed]
2. Schwarz S, Kehrenberg C, Walsh TR. 2001. Use of antimicrobial agents in veterinary medicine and food animal production. Int J Antimicrob Agents 17:431–437 http://dx.doi.org/10.1016/S0924-8579(01)00297-7. [PubMed]
3. Schwarz S, Noble WC. 1999. Aspects of bacterial resistance to antimicrobial agents used in veterinary dermatological practice. Vet Dermatol 10:163–176 http://dx.doi.org/10.1046/j.1365-3164.1999.00170.x.
4. Fiebelkorn KR, Crawford SA, Jorgensen JH. 2005. Mutations in folP associated with elevated sulfonamide MICs for Neisseria meningitidis clinical isolates from five continents. Antimicrob Agents Chemother 49:536–540 http://dx.doi.org/10.1128/AAC.49.2.536-540.2005.
5. Datta N, Hedges RW. 1972. Trimethoprim resistance conferred by W plasmids in Enterobacteriaceae. J Gen Microbiol 72:349–355 http://dx.doi.org/10.1099/00221287-72-2-349. [PubMed]
6. Endtz HP, Ruijs GJ, van Klingeren B, Jansen WH, van der Reyden T, Mouton RP. 1991. Quinolone resistance in campylobacter isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine. J Antimicrob Chemother 27:199–208 http://dx.doi.org/10.1093/jac/27.2.199. [PubMed]
7. Tsiodras S, Gold HS, Sakoulas G, Eliopoulos GM, Wennersten C, Venkataraman L, Moellering RC Jr, Ferraro MJ. 2001. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet 358:207–208 http://dx.doi.org/10.1016/S0140-6736(01)05410-1.
8. Schwarz S, Cloeckaert A, Roberts MC. 2006. Mechanisms and spread of bacterial resistance to antimicrobial agents, p 73–98. In Aarestrup FM (ed), Antimicrobial Resistance in Bacteria of Animal Origin. ASM Press, Washington, DC.
9. Schwarz S, Loeffler A, Kadlec K. 2017. Bacterial resistance to antimicrobial agents and its impact on veterinary and human medicine. Vet Dermatol 28:82–e19 http://dx.doi.org/10.1111/vde.12362. [PubMed]
10. Livermore DM. 1995. β-Lactamases in laboratory and clinical resistance. Clin Microbiol Rev 8:557–584. [PubMed]
11. Georgopapadakou NH. 1993. Penicillin-binding proteins and bacterial resistance to β-lactams. Antimicrob Agents Chemother 37:2045–2053 http://dx.doi.org/10.1128/AAC.37.10.2045. [PubMed]
12. Paulsen IT, Brown MH, Skurray RA. 1996. Proton-dependent multidrug efflux systems. Microbiol Rev 60:575–608. [PubMed]
13. Quintiliani R Jr, Sahm DF, Courvalin P. 1999. Mechanisms of resistance to antimicrobial agents, p 1505–1525. In Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH (ed), Manual of Clinical Microbiology, 7th ed. ASM Press, Washington, DC.
14. Petrosino J, Cantu C III, Palzkill T. 1998. β-Lactamases: protein evolution in real time. Trends Microbiol 6:323–327 http://dx.doi.org/10.1016/S0966-842X(98)01317-1. [PubMed]
15. Bush K. 2001. New beta-lactamases in gram-negative bacteria: diversity and impact on the selection of antimicrobial therapy. Clin Infect Dis 32:1085–1089 http://dx.doi.org/10.1086/319610. [PubMed]
16. Bush K, Jacoby GA, Medeiros AA. 1995. A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 39:1211–1233 http://dx.doi.org/10.1128/AAC.39.6.1211. [PubMed]
17. Ambler RP. 1980. The structure of β-lactamases. Philos Trans R Soc Lond B Biol Sci 289:321–331 http://dx.doi.org/10.1098/rstb.1980.0049. [PubMed]
18. Bush K, Jacoby GA. 2010. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother 54:969–976 http://dx.doi.org/10.1128/AAC.01009-09. [PubMed]
19. Bradford PA. 2001. Extended-spectrum β-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev 14:933–951 http://dx.doi.org/10.1128/CMR.14.4.933-951.2001. [PubMed]
20. Bonnet R. 2004. Growing group of extended-spectrum β-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother 48:1–14 http://dx.doi.org/10.1128/AAC.48.1.1-14.2004. [PubMed]
21. Brolund A, Sandegren L. 2016. Characterization of ESBL disseminating plasmids. Infect Dis (Lond) 48:18–25 http://dx.doi.org/10.3109/23744235.2015.1062536. [PubMed]
22. Weldhagen GF. 2004. Integrons and β-lactamases: a novel perspective on resistance. Int J Antimicrob Agents 23:556–562 http://dx.doi.org/10.1016/j.ijantimicag.2004.03.007. [PubMed]
23. Gilmore KS, Gilmore MS, Sahm DF. 2002. Methicillin resistance in Staphylococcus aureus, p 331–354. In Lewis K, Salyers AA, Taber HW, Wax RG (ed), Bacterial Resistance to Antimicrobials. Marcel Dekker, New York, NY.
24. Hackbarth CJ, Chambers HF. 1989. Methicillin-resistant staphylococci: genetics and mechanisms of resistance. Antimicrob Agents Chemother 33:991–994 http://dx.doi.org/10.1128/AAC.33.7.991. [PubMed]
25. Katayama Y, Ito T, Hiramatsu K. 2000. A new class of genetic element, Staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother 44:1549–1555 http://dx.doi.org/10.1128/AAC.44.6.1549-1555.2000. [PubMed]
27. García-Álvarez L, Holden MT, Lindsay H, Webb CR, Brown DF, Curran MD, Walpole E, Brooks K, Pickard DJ, Teale C, Parkhill J, Bentley SD, Edwards GF, Girvan EK, Kearns AM, Pichon B, Hill RL, Larsen AR, Skov RL, Peacock SJ, Maskell DJ, Holmes MA. 2011. 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 http://dx.doi.org/10.1016/S1473-3099(11)70126-8. [PubMed]
28. Shore AC, Deasy EC, Slickers P, Brennan G, O’Connell B, Monecke S, Ehricht R, Coleman DC. 2011. 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 http://dx.doi.org/10.1128/AAC.00187-11. [PubMed]
29. Loncaric I, Kübber-Heiss A, Posautz A, Stalder GL, Hoffmann D, Rosengarten R, Walzer C. 2013. Characterization of methicillin-resistant Staphylococcus spp. carrying the mecC gene, isolated from wildlife. J Antimicrob Chemother 68:2222–2225 http://dx.doi.org/10.1093/jac/dkt186.
30. Harrison EM, Paterson GK, Holden MT, Morgan FJ, Larsen AR, Petersen A, Leroy S, De Vliegher S, Perreten V, Fox LK, Lam TJ, Sampimon OC, Zadoks RN, Peacock SJ, Parkhill J, Holmes MA. 2013. A Staphylococcus xylosus isolate with a new mecC allotype. Antimicrob Agents Chemother 57:1524–1528 http://dx.doi.org/10.1128/AAC.01882-12. [PubMed]
31. Małyszko I, Schwarz S, Hauschild T. 2014. Detection of a new mecC allotype, mecC2, in methicillin-resistant Staphylococcus saprophyticus. J Antimicrob Chemother 69:2003–2005 http://dx.doi.org/10.1093/jac/dku043. [PubMed]
32. Ehlert K. 1999. Methicillin-resistance in Staphylococcus aureus: molecular basis, novel targets and antibiotic therapy. Curr Pharm Des 5:45–55. [PubMed]
33. Ling B, Berger-Bächi B. 1998. Increased overall antibiotic susceptibility in Staphylococcus aureus femAB null mutants. Antimicrob Agents Chemother 42:936–938. [PubMed]
34. Charrel RN, Pagès J-M, De Micco P, Mallea M. 1996. Prevalence of outer membrane porin alteration in β-lactam-antibiotic-resistant Enterobacter aerogenes. Antimicrob Agents Chemother 40:2854–2858. [PubMed]
35. Hopkins JM, Towner KJ. 1990. Enhanced resistance to cefotaxime and imipenem associated with outer membrane protein alterations in Enterobacter aerogenes. J Antimicrob Chemother 25:49–55 http://dx.doi.org/10.1093/jac/25.1.49. [PubMed]
36. Mitsuyama J, Hiruma R, Yamaguchi A, Sawai T. 1987. Identification of porins in outer membrane of Proteus, Morganella, and Providencia spp. and their role in outer membrane permeation of β-lactams. Antimicrob Agents Chemother 31:379–384 http://dx.doi.org/10.1128/AAC.31.3.379. [PubMed]
37. Simonet V, Malléa M, Pagès J-M. 2000. Substitutions in the eyelet region disrupt cefepime diffusion through the Escherichia coli OmpF channel. Antimicrob Agents Chemother 44:311–315 http://dx.doi.org/10.1128/AAC.44.2.311-315.2000. [PubMed]
38. Martínez-Martínez L, Hernández-Allés S, Albertí S, Tomás 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 40:342–348. [PubMed]
39. Wolter DJ, Hanson ND, Lister PD. 2004. Insertional inactivation of oprD in clinical isolates of Pseudomonas aeruginosa leading to carbapenem resistance. FEMS Microbiol Lett 236:137–143 http://dx.doi.org/10.1111/j.1574-6968.2004.tb09639.x. [PubMed]
40. Poole K. 2002. Multidrug efflux pumps and antimicrobial resistance in Pseudomonas aeruginosa and related organisms, p 273–298. In Paulsen IT, Lewis K (ed), Microbial Multidrug Efflux. Horizon Scientific Press, Wymondham, United Kingdom.
41. Putman M, van Veen HW, Konings WN. 2000. Molecular properties of bacterial multidrug transporters. Microbiol Mol Biol Rev 64:672–693 http://dx.doi.org/10.1128/MMBR.64.4.672-693.2000. [PubMed]
42. Grave K, Torren-Edo J, Muller A, Greko C, Moulin G, Mackay D, Fuchs K, Laurier L, Iliev D, Pokludova L, Genakritis M, Jacobsen E, Kurvits K, Kivilahti-Mantyla K, Wallmann J, Kovacs J, Lenharthsson JM, Beechinor JG, Perrella A, Mičule G, Zymantaite U, Meijering A, Prokopiak D, Ponte MH, Svetlin A, Hederova J, Madero CM, Girma K, Eckford S, ESVAC Group. 2014. Variations in the sales and sales patterns of veterinary antimicrobial agents in 25 European countries. J Antimicrob Chemother 69:2284–2291 http://dx.doi.org/10.1093/jac/dku106. [PubMed]
43. Casas C, Anderson EC, Ojo KK, Keith I, Whelan D, Rainnie D, Roberts MC. 2005. Characterization of pRAS1-like plasmids from atypical North American psychrophilic Aeromonas salmonicida. FEMS Microbiol Lett 242:59–63 http://dx.doi.org/10.1016/j.femsle.2004.10.039. [PubMed]
44. DePaola A, Roberts MC. 1995. Class D and E tetracycline resistance determinants in Gram-negative catfish pond bacteria. Mol Cell Probes 9:311–313 http://dx.doi.org/10.1016/S0890-8508(95)91572-9.
45. Miranda CD, Kehrenberg C, Ulep C, Schwarz S, Roberts MC. 2003. Diversity of tetracycline resistance genes in bacteria from Chilean salmon farms. Antimicrob Agents Chemother 47:883–888 http://dx.doi.org/10.1128/AAC.47.3.883-888.2003. [PubMed]
46. Chopra I, Roberts M. 2001. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev 65:232–260 http://dx.doi.org/10.1128/MMBR.65.2.232-260.2001. [PubMed]
47. Levy SB, McMurry LM, Barbosa TM, Burdett V, Courvalin P, Hillen W, Roberts MC, Rood JI, Taylor DE. 1999. Nomenclature for new tetracycline resistance determinants. Antimicrob Agents Chemother 43:1523–1524. [PubMed]
48. Roberts MC, Schwarz S. 2016. Tetracycline and phenicol resistance genes and mechanisms: importance for agriculture, the environment, and humans. J Environ Qual 45:576–592 http://dx.doi.org/10.2134/jeq2015.04.0207. [PubMed]
49. Roberts MC, Schwarz S, Aarts HJ. 2012. Erratum: acquired antibiotic resistance genes: an overview. Front Microbiol 3:384 http://dx.doi.org/10.3389/fmicb.2012.00384. [PubMed]
50. Roberts MC, No D, Kuchmiy E, Miranda CD. 2015. Tetracycline resistance gene tet(39) identified in three new genera of bacteria isolated in 1999 from Chilean salmon farms. J Antimicrob Chemother 70:619–621 http://dx.doi.org/10.1093/jac/dku412. [PubMed]
51. Speer BS, Shoemaker NB, Salyers AA. 1992. Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. Clin Microbiol Rev 5:387–399 http://dx.doi.org/10.1128/CMR.5.4.387. [PubMed]
52. Linkevicius M, Sandegren L, Andersson DI. 2015. Potential of tetracycline resistance proteins to evolve tigecycline resistance. Antimicrob Agents Chemother 60:789–796 http://dx.doi.org/10.1128/AAC.02465-15. [PubMed]
53. Fiedler S, Bender JK, Klare I, Halbedel S, Grohmann E, Szewzyk U, Werner G. 2016. Tigecycline resistance in clinical isolates of Enterococcus faecium is mediated by an upregulation of plasmid-encoded tetracycline determinants tet(L) and tet(M). J Antimicrob Chemother 71:871–881 http://dx.doi.org/10.1093/jac/dkv420. [PubMed]
54. Roberts MC. 1996. Tetracycline resistance determinants: mechanisms of action, regulation of expression, genetic mobility, and distribution. FEMS Microbiol Rev 19:1–24 http://dx.doi.org/10.1111/j.1574-6976.1996.tb00251.x. [PubMed]
55. Allmeier H, Cresnar B, Greck M, Schmitt R. 1992. Complete nucleotide sequence of Tn 1721: gene organization and a novel gene product with features of a chemotaxis protein. Gene 111:11–20 http://dx.doi.org/10.1016/0378-1119(92)90597-I.
56. Chalmers R, Sewitz S, Lipkow K, Crellin P. 2000. Complete nucleotide sequence of Tn 10. J Bacteriol 182:2970–2972 http://dx.doi.org/10.1128/JB.182.10.2970-2972.2000. [PubMed]
57. Lawley TD, Burland V, Taylor DE. 2000. Analysis of the complete nucleotide sequence of the tetracycline-resistance transposon Tn 10. Plasmid 43:235–239 http://dx.doi.org/10.1006/plas.1999.1458. [PubMed]
58. Kehrenberg C, Werckenthin C, Schwarz S. 1998. Tn 5706, a transposon-like element from Pasteurella multocida mediating tetracycline resistance. Antimicrob Agents Chemother 42:2116–2118. [PubMed]
59. Projan SJ, Kornblum J, Moghazeh SL, Edelman I, Gennaro ML, Novick RP. 1985. Comparative sequence and functional analysis of pT181 and pC221, cognate plasmid replicons from Staphylococcus aureus. Mol Gen Genet 199:452–464 http://dx.doi.org/10.1007/BF00330758. [PubMed]
60. Schwarz S, Noble WC. 1994. Tetracycline resistance genes in staphylococci from the skin of pigs. J Appl Bacteriol 76:320–326 http://dx.doi.org/10.1111/j.1365-2672.1994.tb01635.x. [PubMed]
61. Werckenthin C, Schwarz S, Roberts MC. 1996. Integration of pT181-like tetracycline resistance plasmids into large staphylococcal plasmids involves IS 257. Antimicrob Agents Chemother 40:2542–2544. [PubMed]
62. Taylor DE, Chau A. 1996. Tetracycline resistance mediated by ribosomal protection. Antimicrob Agents Chemother 40:1–5. [PubMed]
63. Connell SR, Tracz DM, Nierhaus KH, Taylor DE. 2003. Ribosomal protection proteins and their mechanism of tetracycline resistance. Antimicrob Agents Chemother 47:3675–3681 http://dx.doi.org/10.1128/AAC.47.12.3675-3681.2003. [PubMed]
64. Flannagan SE, Zitzow LA, Su YA, Clewell DB. 1994. Nucleotide sequence of the 18-kb conjugative transposon Tn 916 from Enterococcus faecalis. Plasmid 32:350–354 http://dx.doi.org/10.1006/plas.1994.1077. [PubMed]
65. Salyers AA, Shoemaker NB, Stevens AM, Li L-Y. 1995. Conjugative transposons: an unusual and diverse set of integrated gene transfer elements. Microbiol Rev 59:579–590. [PubMed]
66. Forsberg KJ, Patel S, Wencewicz TA, Dantas G. 2015. The tetracycline destructases: A novel family of tetracycline-inactivating enzymes. Chem Biol 22:888–897 http://dx.doi.org/10.1016/j.chembiol.2015.05.017. [PubMed]
67. Speer BS, Bedzyk L, Salyers AA. 1991. Evidence that a novel tetracycline resistance gene found on two Bacteroides transposons encodes an NADP-requiring oxidoreductase. J Bacteriol 173:176–183 http://dx.doi.org/10.1128/jb.173.1.176-183.1991. [PubMed]
68. Diaz-Torres ML, McNab R, Spratt DA, Villedieu A, Hunt N, Wilson M, Mullany P. 2003. Novel tetracycline resistance determinant from the oral metagenome. Antimicrob Agents Chemother 47:1430–1432 http://dx.doi.org/10.1128/AAC.47.4.1430-1432.2003. [PubMed]
69. Nonaka L, Suzuki S. 2002. New Mg 2+-dependent oxytetracycline resistance determinant tet 34 in Vibrio isolates from marine fish intestinal contents. Antimicrob Agents Chemother 46:1550–1552 http://dx.doi.org/10.1128/AAC.46.5.1550-1552.2002. [PubMed]
70. Ross JI, Eady EA, Cove JH, Cunliffe WJ. 1998. 16S rRNA mutation associated with tetracycline resistance in a Gram-positive bacterium. Antimicrob Agents Chemother 42:1702–1705. [PubMed]
71. Sutcliffe JA, Leclercq R. 2003. Mechanisms of resistance to macrolides, lincosamides and ketolides, p 281–317. In Schonfeld W, Kirst HA (ed), Macrolide Antibiotics. Birkhauser Verlag, Basel, Switzerland.
72. Schwarz S, Shen J, Kadlec K, Wang Y, Brenner Michael G, Feßler AT, Vester B. 2016. Lincosamides, streptogramins, phenicols, and pleuromutilins: mode of action and mechanisms of resistance. Cold Spring Harb Perspect Med 6:a027037 http://dx.doi.org/10.1101/cshperspect.a027037. [PubMed]
73. Fyfe C, Grossman TH, Kerstein K, Sutcliffe J. 2016. Resistance to macrolide antibiotics in public health pathogens. Cold Spring Harb Perspect Med 6:a025395 http://dx.doi.org/10.1101/cshperspect.a025395. [PubMed]
74. Roberts MC, Sutcliffe J, Courvalin P, Jensen LB, Rood J, Seppala H. 1999. Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob Agents Chemother 43:2823–2830. [PubMed]
75. Leclercq R, Courvalin P. 1991. Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob Agents Chemother 35:1267–1272 http://dx.doi.org/10.1128/AAC.35.7.1267. [PubMed]
76. Weisblum B. 1995. Erythromycin resistance by ribosome modification. Antimicrob Agents Chemother 39:577–585 http://dx.doi.org/10.1128/AAC.39.3.577. [PubMed]
77. Weisblum B. 1995. Insights into erythromycin action from studies of its activity as inducer of resistance. Antimicrob Agents Chemother 39:797–805 http://dx.doi.org/10.1128/AAC.39.4.797. [PubMed]
78. Schmitz F-J, Petridou J, Jagusch H, Astfalk N, Scheuring S, Schwarz S. 2002. Molecular characterization of ketolide-resistant erm(A)-carrying Staphylococcus aureus isolates selected in vitro by telithromycin, ABT-773, quinupristin and clindamycin. J Antimicrob Chemother 49:611–617 http://dx.doi.org/10.1093/jac/49.4.611. [PubMed]
79. Schmitz F-J, Petridou J, Astfalk N, Köhrer K, Scheuring S, Schwarz S. 2002. Molecular analysis of constitutively expressed erm(C) genes selected in vitro by incubation in the presence of the noninducers quinupristin, telithromycin, or ABT-773. Microb Drug Resist 8:171–177 http://dx.doi.org/10.1089/107662902760326878. [PubMed]
80. Lüthje P, Schwarz S. 2007. Molecular analysis of constitutively expressed erm(C) genes selected in vitro in the presence of the non-inducers pirlimycin, spiramycin and tylosin. J Antimicrob Chemother 59:97–101 http://dx.doi.org/10.1093/jac/dkl459. [PubMed]
81. Werckenthin C, Schwarz S, Westh H. 1999. Structural alterations in the translational attenuator of constitutively expressed ermC genes. Antimicrob Agents Chemother 43:1681–1685. [PubMed]
82. Leclercq R, Courvalin P. 1991. Intrinsic and unusual resistance to macrolide, lincosamide, and streptogramin antibiotics in bacteria. Antimicrob Agents Chemother 35:1273–1276 http://dx.doi.org/10.1128/AAC.35.7.1273. [PubMed]
83. Sharkey LK, Edwards TA, O’Neill AJ. 2016. ABC-F proteins mediate antibiotic resistance through ribosomal protection MBio 7:e01975. http://dx.doi.org/10.1128/mBio.01975-15. [PubMed]
84. Ross JI, Eady EA, Cove JH, Cunliffe WJ, Baumberg S, Wootton JC. 1990. Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super-gene family. Mol Microbiol 4:1207–1214 http://dx.doi.org/10.1111/j.1365-2958.1990.tb00696.x. [PubMed]
85. Reynolds E, Ross JI, Cove JH. 2003. Msr(A) and related macrolide/streptogramin resistance determinants: incomplete transporters? Int J Antimicrob Agents 22:228–236 http://dx.doi.org/10.1016/S0924-8579(03)00218-8.
86. Lüthje P, Schwarz S. 2006. Antimicrobial resistance of coagulase-negative staphylococci from bovine subclinical mastitis with particular reference to macrolide-lincosamide resistance phenotypes and genotypes. J Antimicrob Chemother 57:966–969 http://dx.doi.org/10.1093/jac/dkl061. [PubMed]
87. Clancy J, Petitpas J, Dib-Hajj F, Yuan W, Cronan M, Kamath AV, Bergeron J, Retsema JA. 1996. Molecular cloning and functional analysis of a novel macrolide-resistance determinant, mefA, from Streptococcus pyogenes. Mol Microbiol 22:867–879 http://dx.doi.org/10.1046/j.1365-2958.1996.01521.x. [PubMed]
88. Cousin S Jr, Whittington WL, Roberts MC. 2003. Acquired macrolide resistance genes in pathogenic Neisseria spp. isolated between 1940 and 1987. Antimicrob Agents Chemother 47:3877–3880 http://dx.doi.org/10.1128/AAC.47.12.3877-3880.2003. [PubMed]
89. Ojo KK, Ulep C, Van Kirk N, Luis H, Bernardo M, Leitao J, Roberts MC. 2004. The mef(A) gene predominates among seven macrolide resistant genes identified in 13 Gram-negative genera from healthy Portuguese children. Antimicrob Agents Chemother 48:3451–3456 http://dx.doi.org/10.1128/AAC.48.9.3451-3456.2004. [PubMed]
90. Daly MM, Doktor S, Flamm R, Shortridge D. 2004. Characterization and prevalence of MefA, MefE, and the associated msr(D) gene in Streptococcus pneumoniae clinical isolates. J Clin Microbiol 42:3570–3574 http://dx.doi.org/10.1128/JCM.42.8.3570-3574.2004. [PubMed]
91. Plante I, Centrón D, Roy PH. 2003. An integron cassette encoding erythromycin esterase, ere(A), from Providencia stuartii. J Antimicrob Chemother 51:787–790 http://dx.doi.org/10.1093/jac/dkg169. [PubMed]
92. Lipka M, Filipek R, Bochtler M. 2008. Crystal structure and mechanism of the Staphylococcus cohnii virginiamycin B lyase (Vgb). Biochemistry 47:4257–4265 http://dx.doi.org/10.1021/bi7015266. [PubMed]
93. Chesneau O, Tsvetkova K, Courvalin P. 2007. Resistance phenotypes conferred by macrolide phosphotransferases. FEMS Microbiol Lett 269:317–322 http://dx.doi.org/10.1111/j.1574-6968.2007.00643.x. [PubMed]
94. Vester B, Douthwaite S. 2001. Macrolide resistance conferred by base substitutions in 23S rRNA. Antimicrob Agents Chemother 45:1–12 http://dx.doi.org/10.1128/AAC.45.1.1-12.2001. [PubMed]
95. Meier A, Kirschner P, Springer B, Steingrube VA, Brown BA, Wallace RJ Jr, Böttger EC. 1994. Identification of mutations in 23S rRNA gene of clarithromycin-resistant Mycobacterium intracellulare. Antimicrob Agents Chemother 38:381–384 http://dx.doi.org/10.1128/AAC.38.2.381. [PubMed]
96. Karlsson M, Fellström C, Heldtander MU, Johansson KE, Franklin A. 1999. Genetic basis of macrolide and lincosamide resistance in Brachyspira ( Serpulina) hyodysenteriae. FEMS Microbiol Lett 172:255–260 http://dx.doi.org/10.1111/j.1574-6968.1999.tb13476.x. [PubMed]
97. Haanperä M, Huovinen P, Jalava J. 2005. Detection and quantification of macrolide resistance mutations at positions 2058 and 2059 of the 23S rRNA gene by pyrosequencing. Antimicrob Agents Chemother 49:457–460 http://dx.doi.org/10.1128/AAC.49.1.457-460.2005. [PubMed]
98. Harrow SA, Gilpin BJ, Klena JD. 2004. Characterization of erythromycin resistance in Campylobacter coli and Campylobacter jejuni isolated from pig offal in New Zealand. J Appl Microbiol 97:141–148 http://dx.doi.org/10.1111/j.1365-2672.2004.02278.x. [PubMed]
99. Mingeot-Leclercq M-P, Glupczynski Y, Tulkens PM. 1999. Aminoglycosides: activity and resistance. Antimicrob Agents Chemother 43:727–737. [PubMed]
100. 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 57:138–163. [PubMed]
101. Ramirez MS, Tolmasky ME. 2010. Aminoglycoside modifying enzymes. Drug Resist Updat 13:151–171 http://dx.doi.org/10.1016/j.drup.2010.08.003. [PubMed]
102. Wright GD. 1999. Aminoglycoside-modifying enzymes. Curr Opin Microbiol 2:499–503 http://dx.doi.org/10.1016/S1369-5274(99)00007-7. [PubMed]
103. Davies J, Wright GD. 1997. Bacterial resistance to aminoglycoside antibiotics. Trends Microbiol 5:234–240 http://dx.doi.org/10.1016/S0966-842X(97)01033-0.
104. Hedges RW, Shannon KP. 1984. Resistance to apramycin in Escherichia coli isolated from animals: detection of a novel aminoglycoside-modifying enzyme. J Gen Microbiol 130:473–482. [PubMed]
105. Chaslus-Dancla E, Glupcznski Y, Gerbaud G, Lagorce M, Lafont JP, Courvalin P. 1989. Detection of apramycin resistant Enterobacteriaceae in hospital isolates. FEMS Microbiol Lett 52:261–265 http://dx.doi.org/10.1111/j.1574-6968.1989.tb03634.x. [PubMed]
106. Chaslus-Dancla E, Pohl P, Meurisse M, Marin M, Lafont JP. 1991. High genetic homology between plasmids of human and animal origins conferring resistance to the aminoglycosides gentamicin and apramycin. Antimicrob Agents Chemother 35:590–593 http://dx.doi.org/10.1128/AAC.35.3.590. [PubMed]
107. Johnson AP, Burns L, Woodford N, Threlfall EJ, Naidoo J, Cooke EM, George RC. 1994. Gentamicin resistance in clinical isolates of Escherichia coli encoded by genes of veterinary origin. J Med Microbiol 40:221–226 http://dx.doi.org/10.1099/00222615-40-3-221. [PubMed]
108. Lyon BR, Skurray R. 1987. Antimicrobial resistance of Staphylococcus aureus: genetic basis. Microbiol Rev 51:88–134. [PubMed]
109. Rouch DA, Byrne ME, Kong YC, Skurray RA. 1987. The aacA-aphD gentamicin and kanamycin resistance determinant of Tn 4001 from Staphylococcus aureus: expression and nucleotide sequence analysis. J Gen Microbiol 133:3039–3052. [PubMed]
110. Lange CC, Werckenthin C, Schwarz S. 2003. Molecular analysis of the plasmid-borne aacA/aphD resistance gene region of coagulase-negative staphylococci from chickens. J Antimicrob Chemother 51:1397–1401 http://dx.doi.org/10.1093/jac/dkg257. [PubMed]
111. Leelaporn A, Yodkamol K, Waywa D, Pattanachaiwit S. 2008. A novel structure of Tn 4001-truncated element, type V, in clinical enterococcal isolates and multiplex PCR for detecting aminoglycoside resistance genes. Int J Antimicrob Agents 31:250–254 http://dx.doi.org/10.1016/j.ijantimicag.2007.10.019. [PubMed]
112. Recchia GD, Hall RM. 1995. Gene cassettes: a new class of mobile element. Microbiology 141:3015–3027 http://dx.doi.org/10.1099/13500872-141-12-3015. [PubMed]
113. Sandvang D, Aarestrup FM. 2000. Characterization of aminoglycoside resistance genes and class 1 integrons in porcine and bovine gentamicin-resistant Escherichia coli. Microb Drug Resist 6:19–27 http://dx.doi.org/10.1089/mdr.2000.6.19. [PubMed]
114. Feßler AT, Kadlec K, Schwarz S. 2011. Novel apramycin resistance gene apmA in bovine and porcine methicillin-resistant Staphylococcus aureus ST398 isolates. Antimicrob Agents Chemother 55:373–375 http://dx.doi.org/10.1128/AAC.01124-10. [PubMed]
115. Kadlec K, Feßler AT, Couto N, Pomba CF, Schwarz S. 2012. Unusual small plasmids carrying the novel resistance genes dfrK or apmA isolated from methicillin-resistant or -susceptible staphylococci. J Antimicrob Chemother 67:2342–2345 http://dx.doi.org/10.1093/jac/dks235. [PubMed]
116. Feßler AT, Zhao Q, Schoenfelder S, Kadlec K, Brenner Michael G, Wang Y, Ziebuhr W, Shen J, Schwarz S. 2017. Complete sequence of a plasmid from a bovine methicillin-resistant Staphylococcus aureus harbouring a novel ica-like gene cluster in addition to antimicrobial and heavy metal resistance genes. Vet Microbiol 200:95–100 http://dx.doi.org/10.1016/j.vetmic.2016.07.010. [PubMed]
117. Murphy E. 1985. Nucleotide sequence of a spectinomycin adenyltransferase AAD(9) determinant from Staphylococcus aureus and its relationship to AAD(3″) (9). Mol Gen Genet 200:33–39 http://dx.doi.org/10.1007/BF00383309. [PubMed]
118. Wendlandt S, Li B, Lozano C, Ma Z, Torres C, Schwarz S. 2013. Identification of the novel spectinomycin resistance gene spw in methicillin-resistant and methicillin-susceptible Staphylococcus aureus of human and animal origin. J Antimicrob Chemother 68:1679–1680 http://dx.doi.org/10.1093/jac/dkt081. [PubMed]
119. Jamrozy DM, Coldham NG, Butaye P, Fielder MD. 2014. Identification of a novel plasmid-associated spectinomycin adenyltransferase gene spd in methicillin-resistant Staphylococcus aureus ST398 isolated from animal and human sources. J Antimicrob Chemother 69:1193–1196 http://dx.doi.org/10.1093/jac/dkt510. [PubMed]
120. Wendlandt S, Feßler AT, Kadlec K, van Duijkeren E, Schwarz S. 2014. Identification of the novel spectinomycin resistance gene spd in a different plasmid background among methicillin-resistant Staphylococcus aureus CC398 and methicillin-susceptible S. aureus ST433. J Antimicrob Chemother 69:2000–2003 http://dx.doi.org/10.1093/jac/dku067. [PubMed]
121. Wendlandt S, Kadlec K, Schwarz S. 2015. Four novel plasmids from Staphylococcus hyicus and CoNS that carry a variant of the spectinomycin resistance gene spd. J Antimicrob Chemother 70:948–949 http://dx.doi.org/10.1093/jac/dku461. [PubMed]
122. Rosenberg EY, Ma D, Nikaido H. 2000. AcrD of Escherichia coli is an aminoglycoside efflux pump. J Bacteriol 182:1754–1756 http://dx.doi.org/10.1128/JB.182.6.1754-1756.2000. [PubMed]
123. Edgar R, Bibi E. 1997. MdfA, an Escherichia coli multidrug resistance protein with an extraordinarily broad spectrum of drug recognition. J Bacteriol 179:2274–2280 http://dx.doi.org/10.1128/jb.179.7.2274-2280.1997. [PubMed]
124. Salyers AA, Whitt DD. 1994. Bacterial Pathogenesis: a Molecular Approach. ASM Press, Washington, DC.
125. Galimand M, Courvalin P, Lambert T. 2003. Plasmid-mediated high-level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation. Antimicrob Agents Chemother 47:2565–2571 http://dx.doi.org/10.1128/AAC.47.8.2565-2571.2003. [PubMed]
126. Potron A, Poirel L, Nordmann P. 2015. Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: mechanisms and epidemiology. Int J Antimicrob Agents 45:568–585 http://dx.doi.org/10.1016/j.ijantimicag.2015.03.001. [PubMed]
127. Wachino J, Arakawa Y. 2012. Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: an update. Drug Resist Updat 15:133–148 http://dx.doi.org/10.1016/j.drup.2012.05.001. [PubMed]
128. Meier A, Sander P, Schaper KJ, Scholz M, Böttger EC. 1996. Correlation of molecular resistance mechanisms and phenotypic resistance levels in streptomycin-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 40:2452–2454. [PubMed]
129. Prammananan T, Sander P, Brown BA, Frischkorn K, Onyi GO, Zhang Y, Böttger EC, Wallace RJ Jr. 1998. A single 16S ribosomal RNA substitution is responsible for resistance to amikacin and other 2-deoxystreptamine aminoglycosides in Mycobacterium abscessus and Mycobacterium chelonae. J Infect Dis 177:1573–1581 http://dx.doi.org/10.1086/515328. [PubMed]
130. Cohen KA, Bishai WR, Pym AS. 2014. Molecular basis of drug resistance in Mycobacterium tuberculosis. Microbiol Spectr 2: http://dx.doi.org/10.1128/microbiolspec.MGM2-0036-2013. [PubMed]
131. Elwell LP, Fling ME. 1989. Resistance to trimethoprim, p 249–290. In Bryan LE (ed), Microbial Resistance to Drugs. Springer Verlag, Berlin, Germany. http://dx.doi.org/10.1007/978-3-642-74095-4_11
132. Huovinen P. 2001. Resistance to trimethoprim-sulfamethoxazole. Clin Infect Dis 32:1608–1614 http://dx.doi.org/10.1086/320532. [PubMed]
133. Huovinen P, Sundström L, Swedberg G, Sköld O. 1995. Trimethoprim and sulfonamide resistance. Antimicrob Agents Chemother 39:279–289 http://dx.doi.org/10.1128/AAC.39.2.279. [PubMed]
134. Sköld O. 2000. Sulfonamide resistance: mechanisms and trends. Drug Resist Updat 3:155–160 http://dx.doi.org/10.1054/drup.2000.0146. [PubMed]
135. Sköld O. 2001. Resistance to trimethoprim and sulfonamides. Vet Res 32:261–273 http://dx.doi.org/10.1051/vetres:2001123. [PubMed]
136. Köhler T, Kok M, Michea-Hamzehpour M, Plesiat P, Gotoh N, Nishino T, Curty LK, Pechere J-C. 1996. Multidrug efflux in intrinsic resistance to trimethoprim and sulfamethoxazole in Pseudomonas aeruginosa. Antimicrob Agents Chemother 40:2288–2290. [PubMed]
137. Padayachee T, Klugman KP. 1999. Novel expansions of the gene encoding dihydropteroate synthase in trimethoprim-sulfamethoxazole-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother 43:2225–2230. [PubMed]
138. Dale GE, Broger C, D’Arcy A, Hartman PG, DeHoogt R, Jolidon S, Kompis I, Labhardt AM, Langen H, Locher H, Page MG, Stüber D, Then RL, Wipf B, Oefner C. 1997. A single amino acid substitution in Staphylococcus aureus dihydrofolate reductase determines trimethoprim resistance. J Mol Biol 266:23–30 http://dx.doi.org/10.1006/jmbi.1996.0770. [PubMed]
139. Pikis A, Donkersloot JA, Rodriguez WJ, Keith JM. 1998. A conservative amino acid mutation in the chromosome-encoded dihydrofolate reductase confers trimethoprim resistance in Streptococcus pneumoniae. J Infect Dis 178:700–706 http://dx.doi.org/10.1086/515371. [PubMed]
140. de Groot R, Sluijter M, de Bruyn A, Campos J, Goessens WHF, Smith AL, Hermans PWM. 1996. Genetic characterization of trimethoprim resistance in Haemophilus influenzae. Antimicrob Agents Chemother 40:2131–2136. [PubMed]
141. Sundström L, Rådström P, Swedberg G, Sköld O. 1988. Site-specific recombination promotes linkage between trimethoprim- and sulfonamide resistance genes. Sequence characterization of dhfrV and sulI and a recombination active locus of Tn 21. Mol Gen Genet 213:191–201 http://dx.doi.org/10.1007/BF00339581. [PubMed]
142. Rådström P, Swedberg G. 1988. RSF1010 and a conjugative plasmid contain sulII, one of two known genes for plasmid-borne sulfonamide resistance dihydropteroate synthase. Antimicrob Agents Chemother 32:1684–1692 http://dx.doi.org/10.1128/AAC.32.11.1684. [PubMed]
143. Swedberg G, Sköld O. 1980. Characterization of different plasmid-borne dihydropteroate synthases mediating bacterial resistance to sulfonamides. J Bacteriol 142:1–7. [PubMed]
144. Perreten V, Boerlin P. 2003. A new sulfonamide resistance gene ( sul3) in Escherichia coli is widespread in the pig population of Switzerland. Antimicrob Agents Chemother 47:1169–1172 http://dx.doi.org/10.1128/AAC.47.3.1169-1172.2003. [PubMed]
145. Grape M, Sundström L, Kronvall G. 2003. Sulphonamide resistance gene sul3 found in Escherichia coli isolates from human sources. J Antimicrob Chemother 52:1022–1024 http://dx.doi.org/10.1093/jac/dkg473. [PubMed]
146. Guerra B, Junker E, Helmuth R. 2004. Incidence of the recently described sulfonamide resistance gene sul3 among German Salmonella enterica strains isolated from livestock and food. Antimicrob Agents Chemother 48:2712–2715 http://dx.doi.org/10.1128/AAC.48.7.2712-2715.2004. [PubMed]
147. Guerra B, Junker E, Schroeter A, Malorny B, Lehmann S, Helmuth R. 2003. Phenotypic and genotypic characterization of antimicrobial resistance in German Escherichia coli isolates from cattle, swine and poultry. J Antimicrob Chemother 52:489–492 http://dx.doi.org/10.1093/jac/dkg362.
148. Pattishall KH, Acar J, Burchall JJ, Goldstein FW, Harvey RJ. 1977. Two distinct types of trimethoprim-resistant dihydrofolate reductase specified by R-plasmids of different compatibility groups. J Biol Chem 252:2319–2323. [PubMed]
149. Sekiguchi J, Tharavichitkul P, Miyoshi-Akiyama T, Chupia V, Fujino T, Araake M, Irie A, Morita K, Kuratsuji T, Kirikae T. 2005. Cloning and characterization of a novel trimethoprim-resistant dihydrofolate reductase from a nosocomial isolate of Staphylococcus aureus CM.S2 (IMCJ1454). Antimicrob Agents Chemother 49:3948–3951 http://dx.doi.org/10.1128/AAC.49.9.3948-3951.2005. [PubMed]
150. Dale GE, Langen H, Page MG, Then RL, Stüber D. 1995. Cloning and characterization of a novel, plasmid-encoded trimethoprim-resistant dihydrofolate reductase from Staphylococcus haemolyticus MUR313. Antimicrob Agents Chemother 39:1920–1924 http://dx.doi.org/10.1128/AAC.39.9.1920. [PubMed]
151. Charpentier E, Courvalin P. 1997. Emergence of the trimethoprim resistance gene dfrD in Listeria monocytogenes BM4293. Antimicrob Agents Chemother 41:1134–1136. [PubMed]
152. Kadlec K, Schwarz S. 2009. Identification of a novel trimethoprim resistance gene, dfrK, in a methicillin-resistant Staphylococcus aureus ST398 strain and its physical linkage to the tetracycline resistance gene tet(L). Antimicrob Agents Chemother 53:776–778 http://dx.doi.org/10.1128/AAC.01128-08. [PubMed]
153. Kadlec K, Schwarz S. 2010. Identification of the novel dfrK-carrying transposon Tn 559 in a porcine methicillin-susceptible Staphylococcus aureus ST398 strain. Antimicrob Agents Chemother 54:3475–3477 http://dx.doi.org/10.1128/AAC.00464-10. [PubMed]
154. López M, Kadlec K, Schwarz S, Torres C. 2012. First detection of the staphylococcal trimethoprim resistance gene dfrK and the dfrK-carrying transposon Tn 559 in enterococci. Microb Drug Resist 18:13–18 http://dx.doi.org/10.1089/mdr.2011.0073. [PubMed]
155. Rouch DA, Messerotti LJ, Loo LSL, Jackson CA, Skurray RA. 1989. Trimethoprim resistance transposon Tn 4003 from Staphylococcus aureus encodes genes for a dihydrofolate reductase and thymidylate synthetase flanked by three copies of IS 257. Mol Microbiol 3:161–175 http://dx.doi.org/10.1111/j.1365-2958.1989.tb01805.x. [PubMed]
156. Kehrenberg C, Schwarz S. 2005. dfrA20, a novel trimethoprim resistance gene from Pasteurella multocida. Antimicrob Agents Chemother 49:414–417 http://dx.doi.org/10.1128/AAC.49.1.414-417.2005. [PubMed]
157. Webber M, Piddock LJV. 2001. Quinolone resistance in Escherichia coli. Vet Res 32:275–284 http://dx.doi.org/10.1051/vetres:2001124. [PubMed]
158. Bager F, Helmuth R. 2001. Epidemiology of quinolone resistance in Salmonella. Vet Res 32:285–290 http://dx.doi.org/10.1051/vetres:2001125. [PubMed]
159. Drlica K, Zhao X. 1997. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 61:377–392. [PubMed]
160. Everett MJ, Piddock LJV. 1998. Mechanisms of resistance to fluoroquinolones, p 259–296. In Kuhlmann J, Dalhoff A, Zeiler H-J (ed), Quinolone Antibacterials. Springer Verlag, Berlin, Germany. http://dx.doi.org/10.1007/978-3-642-80364-2_9
161. Hooper DC. 1999. Mechanisms of fluoroquinolone resistance. Drug Resist Updat 2:38–55 http://dx.doi.org/10.1054/drup.1998.0068. [PubMed]
162. Ruiz J. 2003. Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection. J Antimicrob Chemother 51:1109–1117 http://dx.doi.org/10.1093/jac/dkg222. [PubMed]
163. Guan X, Xue X, Liu Y, Wang J, Wang Y, Wang J, Wang K, Jiang H, Zhang L, Yang B, Wang N, Pan L. 2013. Plasmid-mediated quinolone resistance: current knowledge and future perspectives. J Int Med Res 41:20–30 http://dx.doi.org/10.1177/0300060513475965. [PubMed]
164. Yoshida H, Bogaki M, Nakamura M, Nakamura S. 1990. Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob Agents Chemother 34:1271–1272 http://dx.doi.org/10.1128/AAC.34.6.1271. [PubMed]
165. Cloeckaert A, Chaslus-Dancla E. 2001. Mechanisms of quinolone resistance in Salmonella. Vet Res 32:291–300 http://dx.doi.org/10.1051/vetres:2001105. [PubMed]
166. Jones ME, Sahm DF, Martin N, Scheuring S, Heisig P, Thornsberry C, Köhrer K, Schmitz F-J. 2000. Prevalence of gyrA, gyrB, parC, and parE mutations in clinical isolates of Streptococcus pneumoniae with decreased susceptibilities to different fluoroquinolones and originating from worldwide surveillance studies during the 1997-1998 respiratory season. Antimicrob Agents Chemother 44:462–466 http://dx.doi.org/10.1128/AAC.44.2.462-466.2000. [PubMed]
167. Everett MJ, Jin YF, Ricci V, Piddock LJV. 1996. Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. Antimicrob Agents Chemother 40:2380–2386. [PubMed]
168. Poole K. 2000. Efflux-mediated resistance to fluoroquinolones in Gram-negative bacteria. Antimicrob Agents Chemother 44:2233–2241 http://dx.doi.org/10.1128/AAC.44.9.2233-2241.2000. [PubMed]
169. Poole K. 2000. Efflux-mediated resistance to fluoroquinolones in Gram-positive bacteria and the mycobacteria. Antimicrob Agents Chemother 44:2595–2599 http://dx.doi.org/10.1128/AAC.44.10.2595-2599.2000. [PubMed]
170. Alekshun MN, Levy SB. 1999. The mar regulon: multiple resistance to antibiotics and other toxic chemicals. Trends Microbiol 7:410–413 http://dx.doi.org/10.1016/S0966-842X(99)01589-9.
171. Okusu H, Ma D, Nikaido H. 1996. AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants. J Bacteriol 178:306–308 http://dx.doi.org/10.1128/jb.178.1.306-308.1996. [PubMed]
172. Olliver A, Vallé M, Chaslus-Dancla E, Cloeckaert A. 2004. 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 http://dx.doi.org/10.1016/j.femsle.2004.07.046. [PubMed]
173. Oethinger M, Podglajen I, Kern WV, Levy SB. 1998. Overexpression of the marA or soxS regulatory gene in clinical topoisomerase mutants of Escherichia coli. Antimicrob Agents Chemother 42:2089–2094. [PubMed]
174. Barbosa TM, Levy SB. 2000. Differential expression of over 60 chromosomal genes in Escherichia coli by constitutive expression of MarA. J Bacteriol 182:3467–3474 http://dx.doi.org/10.1128/JB.182.12.3467-3474.2000. [PubMed]
175. 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 182:3142–3150 http://dx.doi.org/10.1128/JB.182.11.3142-3150.2000. [PubMed]
176. Oethinger M, Kern WV, Jellen-Ritter AS, McMurry LM, Levy SB. 2000. Ineffectiveness of topoisomerase mutations in mediating clinically significant fluoroquinolone resistance in Escherichia coli in the absence of the AcrAB efflux pump. Antimicrob Agents Chemother 44:10–13 http://dx.doi.org/10.1128/AAC.44.1.10-13.2000. [PubMed]
177. Lomovskaya O, Lee A, Hoshino K, Ishida H, Mistry A, Warren MS, Boyer E, Chamberland S, Lee VJ. 1999. Use of a genetic approach to evaluate the consequences of inhibition of efflux pumps in Pseudomonas aeruginosa. Antimicrob Agents Chemother 43:1340–1346. [PubMed]
178. Baucheron S, Chaslus-Dancla E, Cloeckaert A. 2004. Role of TolC and parC mutation in high-level fluoroquinolone resistance in Salmonella enterica serotype Typhimurium DT204. J Antimicrob Chemother 53:657–659 http://dx.doi.org/10.1093/jac/dkh122. [PubMed]
179. Baucheron S, Imberechts H, Chaslus-Dancla E, Cloeckaert A. 2002. The AcrB multidrug transporter plays a major role in high-level fluoroquinolone resistance in Salmonella enterica serovar Typhimurium phage type DT204. Microb Drug Resist 8:281–289 http://dx.doi.org/10.1089/10766290260469543. [PubMed]
180. Cohen SP, McMurry LM, Levy SB. 1988. marA locus causes decreased expression of OmpF porin in multiple-antibiotic-resistant (Mar) mutants of Escherichia coli. J Bacteriol 170:5416–5422 http://dx.doi.org/10.1128/jb.170.12.5416-5422.1988. [PubMed]
181. McMurry LM, George AM, Levy SB. 1994. Active efflux of chloramphenicol in susceptible Escherichia coli strains and in multiple-antibiotic-resistant (Mar) mutants. Antimicrob Agents Chemother 38:542–546 http://dx.doi.org/10.1128/AAC.38.3.542. [PubMed]
182. Hooper DC, Wolfson JS, Bozza MA, Ng EY. 1992. Genetics and regulation of outer membrane protein expression by quinolone resistance loci nfxB, nfxC, and cfxB. Antimicrob Agents Chemother 36:1151–1154 http://dx.doi.org/10.1128/AAC.36.5.1151.
183. Juárez-Verdayes MA, Parra-Ortega B, Hernández-Rodríguez C, Betanzos-Cabrera G, Rodríguez-Martínez S, Cancino-Diaz ME, Cancino-Diaz JC. 2012. Identification and expression of nor efflux family genes in Staphylococcus epidermidis that act against gatifloxacin. Microb Pathog 52:318–325 http://dx.doi.org/10.1016/j.micpath.2012.03.001. [PubMed]
184. Tran JH, Jacoby GA. 2002. Mechanism of plasmid-mediated quinolone resistance. Proc Natl Acad Sci USA 99:5638–5642 http://dx.doi.org/10.1073/pnas.082092899. [PubMed]
185. Jacoby GA, Strahilevitz J, Hooper DC. 2014. Plasmid-mediated quinolone resistance. Microbiol Spectrum 2:PLAS-0006-2013
186. Rodríguez-Martínez JM, Machuca J, Cano ME, Calvo J, Martínez-Martínez L, Pascual A. 2016. Plasmid-mediated quinolone resistance: two decades on. Drug Resist Updat 29:13–29 http://dx.doi.org/10.1016/j.drup.2016.09.001. [PubMed]
187. Murray IA, Shaw WV. 1997. O-Acetyltransferases for chloramphenicol and other natural products. Antimicrob Agents Chemother 41:1–6. [PubMed]
188. Schwarz S, Kehrenberg C, Doublet B, Cloeckaert A. 2004. Molecular basis of bacterial resistance to chloramphenicol and florfenicol. FEMS Microbiol Rev 28:519–542 http://dx.doi.org/10.1016/j.femsre.2004.04.001. [PubMed]
189. Shaw WV. 1983. Chloramphenicol acetyltransferase: enzymology and molecular biology. CRC Crit Rev Biochem 14:1–46 http://dx.doi.org/10.3109/10409238309102789. [PubMed]
190. Alekshun MN, Levy SB. 2000. Bacterial drug resistance: response to survival threats, p 323–366. In Storz G, Hengge-Aronis R (ed), Bacterial Stress Responses. ASM Press, Washington, DC.
191. Alton NK, Vapnek D. 1979. Nucleotide sequence analysis of the chloramphenicol resistance transposon Tn 9. Nature 282:864–869 http://dx.doi.org/10.1038/282864a0. [PubMed]
192. Murray IA, Hawkins AR, Keyte JW, Shaw WV. 1988. Nucleotide sequence analysis and overexpression of the gene encoding a type III chloramphenicol acetyltransferase. Biochem J 252:173–179 http://dx.doi.org/10.1042/bj2520173. [PubMed]
193. 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 272:505–510 http://dx.doi.org/10.1042/bj2720505. [PubMed]
194. Brenner DG, Shaw WV. 1985. The use of synthetic oligonucleotides with universal templates for rapid DNA sequencing: results with staphylococcal replicon pC221. EMBO J 4:561–568. [PubMed]
195. Horinouchi S, Weisblum B. 1982. Nucleotide sequence and functional map of pC194, a plasmid that specifies inducible chloramphenicol resistance. J Bacteriol 150:815–825. [PubMed]
196. Schwarz S, Cardoso M. 1991. Nucleotide sequence and phylogeny of a chloramphenicol acetyltransferase encoded by the plasmid pSCS7 from Staphylococcus aureus. Antimicrob Agents Chemother 35:1551–1556 http://dx.doi.org/10.1128/AAC.35.8.1551. [PubMed]
197. Lovett PS. 1990. Translational attenuation as the regulator of inducible cat genes. J Bacteriol 172:1–6 http://dx.doi.org/10.1128/jb.172.1.1-6.1990. [PubMed]
198. Bannam TL, Rood JI. 1991. Relationship between the Clostridium perfringens catQ gene product and chloramphenicol acetyltransferases from other bacteria. Antimicrob Agents Chemother 35:471–476 http://dx.doi.org/10.1128/AAC.35.3.471. [PubMed]
199. Lang KS, Anderson JM, Schwarz S, Williamson L, Handelsman J, Singer RS. 2010. Novel florfenicol and chloramphenicol resistance gene discovered in Alaskan soil by using functional metagenomics. Appl Environ Microbiol 76:5321–5326 http://dx.doi.org/10.1128/AEM.00323-10. [PubMed]
200. Stokes HW, Hall RM. 1991. Sequence analysis of the inducible chloramphenicol resistance determinant in the Tn 1696 integron suggests regulation by translational attenuation. Plasmid 26:10–19 http://dx.doi.org/10.1016/0147-619X(91)90032-R.
201. Cloeckaert A, Baucheron S, Chaslus-Dancla E. 2001. Nonenzymatic chloramphenicol resistance mediated by IncC plasmid R55 is encoded by a floR gene variant. Antimicrob Agents Chemother 45:2381–2382 http://dx.doi.org/10.1128/AAC.45.8.2381-2382.2001. [PubMed]
202. Cloeckaert A, Baucheron S, Flaujac G, Schwarz S, Kehrenberg C, Martel JL, Chaslus-Dancla E. 2000. Plasmid-mediated florfenicol resistance encoded by the floR gene in Escherichia coli isolated from cattle. Antimicrob Agents Chemother 44:2858–2860 http://dx.doi.org/10.1128/AAC.44.10.2858-2860.2000. [PubMed]
203. Hochhut B, Lotfi Y, Mazel D, Faruque SM, Woodgate R, Waldor MK. 2001. Molecular analysis of antibiotic resistance gene clusters in Vibrio cholerae O139 and O1 SXT constins. Antimicrob Agents Chemother 45:2991–3000 http://dx.doi.org/10.1128/AAC.45.11.2991-3000.2001. [PubMed]
204. Kehrenberg C, Schwarz S. 2005. Plasmid-borne florfenicol resistance in Pasteurella multocida. J Antimicrob Chemother 55:773–775 http://dx.doi.org/10.1093/jac/dki102. [PubMed]
205. Keyes K, Hudson C, Maurer JJ, Thayer S, White DG, Lee MD. 2000. Detection of florfenicol resistance genes in Escherichia coli isolated from sick chickens. Antimicrob Agents Chemother 44:421–424 http://dx.doi.org/10.1128/AAC.44.2.421-424.2000. [PubMed]
206. Kim E, Aoki T. 1996. Sequence analysis of the florfenicol resistance gene encoded in the transferable R-plasmid of a fish pathogen, Pasteurella piscicida. Microbiol Immunol 40:665–669 http://dx.doi.org/10.1111/j.1348-0421.1996.tb01125.x. [PubMed]
207. 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 38:4593–4598. [PubMed]
208. Michael GB, Kadlec K, Sweeney MT, Brzuszkiewicz E, Liesegang H, Daniel R, Murray RW, Watts JL, Schwarz S. 2012. ICE Pmu1, an integrative conjugative element (ICE) of Pasteurella multocida: analysis of the regions that comprise 12 antimicrobial resistance genes. J Antimicrob Chemother 67:84–90 http://dx.doi.org/10.1093/jac/dkr406. [PubMed]
209. Hall RM. 2010. Salmonella genomic islands and antibiotic resistance in Salmonella enterica. Future Microbiol 5:1525–1538 http://dx.doi.org/10.2217/fmb.10.122. [PubMed]
210. He T, Shen J, Schwarz S, Wu C, Wang Y. 2015. Characterization of a genomic island in Stenotrophomonas maltophilia that carries a novel floR gene variant. J Antimicrob Chemother 70:1031–1036 http://dx.doi.org/10.1093/jac/dku491. [PubMed]
211. Kehrenberg C, Schwarz S. 2004. fexA, a novel Staphylococcus lentus gene encoding resistance to florfenicol and chloramphenicol. Antimicrob Agents Chemother 48:615–618 http://dx.doi.org/10.1128/AAC.48.2.615-618.2004. [PubMed]
212. Kehrenberg C, Schwarz S. 2005. Florfenicol-chloramphenicol exporter gene fexA is part of the novel transposon Tn558. Antimicrob Agents Chemother 49:813–815 http://dx.doi.org/10.1128/AAC.49.2.813-815.2005. [PubMed]
213. Liu H, Wang Y, Wu C, Schwarz S, Shen Z, Jeon B, Ding S, Zhang Q, Shen J. 2012. A novel phenicol exporter gene, fexB, found in enterococci of animal origin. J Antimicrob Chemother 67:322–325 http://dx.doi.org/10.1093/jac/dkr481. [PubMed]
214. Ettayebi M, Prasad SM, Morgan EA. 1985. Chloramphenicol-erythromycin resistance mutations in a 23S rRNA gene of Escherichia coli. J Bacteriol 162:551–557. [PubMed]
215. Long KS, Vester B. 2012. Resistance to linezolid caused by modifications at its binding site on the ribosome. Antimicrob Agents Chemother 56:603–612 http://dx.doi.org/10.1128/AAC.05702-11. [PubMed]
216. Mendes RE, Deshpande LM, Farrell DJ, Spanu T, Fadda G, Jones RN. 2010. Assessment of linezolid resistance mechanisms among Staphylococcus epidermidis causing bacteraemia in Rome, Italy. J Antimicrob Chemother 65:2329–2335 http://dx.doi.org/10.1093/jac/dkq331.
217. Shaw KJ, Barbachyn MR. 2011. The oxazolidinones: past, present, and future. Ann N Y Acad Sci 1241:48–70 http://dx.doi.org/10.1111/j.1749-6632.2011.06330.x. [PubMed]
218. Locke JB, Hilgers M, Shaw KJ. 2009. Mutations in ribosomal protein L3 are associated with oxazolidinone resistance in staphylococci of clinical origin. Antimicrob Agents Chemother 53:5275–5278 http://dx.doi.org/10.1128/AAC.01032-09. [PubMed]
219. 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 49:3554–3557 http://dx.doi.org/10.1128/AAC.49.8.3554-3557.2005. [PubMed]
220. Shore AC, Lazaris A, Kinnevey PM, Brennan OM, Brennan GI, O’Connell B, Feßler AT, Schwarz S, Coleman DC. 2016. First report of cfr-carrying plasmids in the pandemic sequence type 22 methicillin-resistant Staphylococcus aureus staphylococcal cassette chromosome mec type IV clone. Antimicrob Agents Chemother 60:3007–3015 http://dx.doi.org/10.1128/AAC.02949-15. [PubMed]
221. Schwarz S, Werckenthin C, Kehrenberg C. 2000. Identification of a plasmid-borne chloramphenicol-florfenicol resistance gene in Staphylococcus sciuri. Antimicrob Agents Chemother 44:2530–2533 http://dx.doi.org/10.1128/AAC.44.9.2530-2533.2000. [PubMed]
222. Kehrenberg C, Schwarz S, Jacobsen L, Hansen LH, Vester B. 2005. A new mechanism for chloramphenicol, florfenicol and clindamycin resistance: methylation of 23S ribosomal RNA at A2503. Mol Microbiol 57:1064–1073 http://dx.doi.org/10.1111/j.1365-2958.2005.04754.x. [PubMed]
223. Long KS, Poehlsgaard J, Kehrenberg C, Schwarz S, Vester B. 2006. The Cfr rRNA methyltransferase confers resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics. Antimicrob Agents Chemother 50:2500–2505 http://dx.doi.org/10.1128/AAC.00131-06. [PubMed]
224. Shen J, Wang Y, Schwarz S. 2013. Presence and dissemination of the multiresistance gene cfr in Gram-positive and Gram-negative bacteria. J Antimicrob Chemother 68:1697–1706 http://dx.doi.org/10.1093/jac/dkt092. [PubMed]
225. Wang Y, Li D, Song L, Liu Y, He T, Liu H, Wu C, Schwarz S, Shen J. 2013. First report of the multiresistance gene cfr in Streptococcus suis. Antimicrob Agents Chemother 57:4061–4063 http://dx.doi.org/10.1128/AAC.00713-13. [PubMed]
226. Hansen LH, Vester B. 2015. A cfr-like gene from Clostridium difficile confers multiple antibiotic resistance by the same mechanism as the cfr gene. Antimicrob Agents Chemother 59:5841–5843 http://dx.doi.org/10.1128/AAC.01274-15. [PubMed]
227. Deshpande LM, Ashcraft DS, Kahn HP, Pankey G, Jones RN, Farrell DJ, Mendes RE. 2015. Detection of a new cfr-like gene, cfr(B), in Enterococcus faecium isolates recovered from human specimens in the United States as part of the SENTRY antimicrobial surveillance program. Antimicrob Agents Chemother 59:6256–6261 http://dx.doi.org/10.1128/AAC.01473-15. [PubMed]
228. Tang Y, Dai L, Sahin O, Wu Z, Liu M, Zhang Q. 2017. Emergence of a plasmid-borne multidrug resistance gene cfr(C) in foodborne pathogen Campylobacter. J Antimicrob Chemother 72:1581–1588 http://dx.doi.org/10.1093/jac/dkx023. [PubMed]
229. Wang Y, Lv Y, Cai J, Schwarz S, Cui L, Hu Z, Zhang R, Li J, Zhao Q, He T, Wang D, Wang Z, Shen Y, Li Y, Feßler AT, Wu C, Yu H, Deng X, Xia X, Shen J. 2015. A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in Enterococcus faecalis and Enterococcus faecium of human and animal origin. J Antimicrob Chemother 70:2182–2190 http://dx.doi.org/10.1093/jac/dkv116. [PubMed]
230. He T, Shen Y, Schwarz S, Cai J, Lv Y, Li J, Feßler AT, Zhang R, Wu C, Shen J, Wang Y. 2016. Genetic environment of the transferable oxazolidinone/phenicol resistance gene optrA in Enterococcus faecalis isolates of human and animal origin. J Antimicrob Chemother 71:1466–1473 http://dx.doi.org/10.1093/jac/dkw016. [PubMed]
231. Li D, Wang Y, Schwarz S, Cai J, Fan R, Li J, Feßler AT, Zhang R, Wu C, Shen J. 2016. Co-location of the oxazolidinone resistance genes optrA and cfr on a multiresistance plasmid from Staphylococcus sciuri. J Antimicrob Chemother 71:1474–1478 http://dx.doi.org/10.1093/jac/dkw040. [PubMed]
232. Fan R, Li D, Wang Y, He T, Feßler AT, Schwarz S, Wu C. 2016. Presence of the optrA gene in methicillin-resistant Staphylococcus sciuri of porcine origin. Antimicrob Agents Chemother 60:7200–7205 http://dx.doi.org/10.1128/AAC.01591-16. [PubMed]
233. Huang J, Chen L, Wu Z, Wang L. 2017. Retrospective analysis of genome sequences revealed the wide dissemination of optrA in Gram-positive bacteria. J Antimicrob Chemother 72:614–616 http://dx.doi.org/10.1093/jac/dkw488. [PubMed]
234. Arthur M, Reynolds P, Courvalin P. 1996. Glycopeptide resistance in enterococci. Trends Microbiol 4:401–407 http://dx.doi.org/10.1016/0966-842X(96)10063-9. [PubMed]
235. Walsh C. 2003. Antibiotics: Actions, Origins, Resistance. ASM Press, Washington, DC. http://dx.doi.org/10.1128/9781555817886
236. Gudeta DD, Moodley A, Bortolaia V, Guardabassi L. 2014. vanO, a new glycopeptide resistance operon in environmental Rhodococcus equi isolates. Antimicrob Agents Chemother 58:1768–1770 http://dx.doi.org/10.1128/AAC.01880-13. [PubMed]
237. Arthur M, Molinas C, Depardieu F, Courvalin P. 1993. Characterization of Tn 1546, a Tn 3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J Bacteriol 175:117–127 http://dx.doi.org/10.1128/jb.175.1.117-127.1993. [PubMed]
238. Aarestrup FM. 1995. Occurrence of glycopeptide resistance among Enterococcus faecium isolates from conventional and ecological poultry farms. Microb Drug Resist 1:255–257 http://dx.doi.org/10.1089/mdr.1995.1.255. [PubMed]
239. Klare I, Heier H, Claus H, Reissbrodt R, Witte W. 1995. vanA-mediated high-level glycopeptide resistance in Enterococcus faecium from animal husbandry. FEMS Microbiol Lett 125:165–171 http://dx.doi.org/10.1111/j.1574-6968.1995.tb07353.x. [PubMed]
240. Noble WC, Virani Z, Cree RG. 1992. Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiol Lett 72:195–198 http://dx.doi.org/10.1111/j.1574-6968.1992.tb05089.x. [PubMed]
241. 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 302:1569–1571 http://dx.doi.org/10.1126/science.1090956. [PubMed]
242. Guardabassi L, Christensen H, Hasman H, Dalsgaard A. 2004. Members of the genera Paenibacillus and Rhodococcus harbor genes homologous to enterococcal glycopeptide resistance genes vanA and vanB. Antimicrob Agents Chemother 48:4915–4918 http://dx.doi.org/10.1128/AAC.48.12.4915-4918.2004. [PubMed]
243. Wendlandt S, Shen J, Kadlec K, Wang Y, Li B, Zhang WJ, Feßler AT, Wu C, Schwarz S. 2015. Multidrug resistance genes in staphylococci from animals that confer resistance to critically and highly important antimicrobial agents in human medicine. Trends Microbiol 23:44–54 http://dx.doi.org/10.1016/j.tim.2014.10.002. [PubMed]
244. Wendlandt S, Kadlec K, Feßler AT, Schwarz S. 2015. Identification of ABC transporter genes conferring combined pleuromutilin-lincosamide-streptogramin A resistance in bovine methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci. Vet Microbiol 177:353–358 http://dx.doi.org/10.1016/j.vetmic.2015.03.027. [PubMed]
245. Pringle M, Poehlsgaard J, Vester B, Long KS. 2004. Mutations in ribosomal protein L3 and 23S ribosomal RNA at the peptidyl transferase centre are associated with reduced susceptibility to tiamulin in Brachyspira spp. isolates. Mol Microbiol 54:1295–1306 http://dx.doi.org/10.1111/j.1365-2958.2004.04373.x. [PubMed]
246. Hidalgo Á, Carvajal A, Vester B, Pringle M, Naharro G, Rubio P. 2011. Trends towards lower antimicrobial susceptibility and characterization of acquired resistance among clinical isolates of Brachyspira hyodysenteriae in Spain. Antimicrob Agents Chemother 55:3330–3337 http://dx.doi.org/10.1128/AAC.01749-10. [PubMed]
247. Pringle M, Landén A, Unnerstad HE, Molander B, Bengtsson B. 2012. Antimicrobial susceptibility of porcine Brachyspira hyodysenteriae and Brachyspira pilosicoli isolated in Sweden between 1990 and 2010. Acta Vet Scand 54:54 http://dx.doi.org/10.1186/1751-0147-54-54. [PubMed]
248. Li BB, Shen JZ, Cao XY, Wang Y, Dai L, Huang SY, Wu CM. 2010. Mutations in 23S rRNA gene associated with decreased susceptibility to tiamulin and valnemulin in Mycoplasma gallisepticum. FEMS Microbiol Lett 308:144–149 http://dx.doi.org/10.1111/j.1574-6968.2010.02003.x.
249. van Duijkeren E, Greko C, Pringle M, Baptiste KE, Catry B, Jukes H, Moreno MA, Pomba MC, Pyörälä S, Rantala M, Ružauskas M, Sanders P, Teale C, Threlfall EJ, Torren-Edo J, Törneke K. 2014. Pleuromutilins: use in food-producing animals in the European Union, development of resistance and impact on human and animal health. J Antimicrob Chemother 69:2022–2031 http://dx.doi.org/10.1093/jac/dku123. [PubMed]
250. Isnard C, Malbruny B, Leclercq R, Cattoir V. 2013. Genetic basis for in vitro and in vivo resistance to lincosamides, streptogramins A, and pleuromutilins (LS AP phenotype) in Enterococcus faecium. Antimicrob Agents Chemother 57:4463–4469 http://dx.doi.org/10.1128/AAC.01030-13. [PubMed]
251. Wendlandt S, Lozano C, Kadlec K, Gómez-Sanz E, Zarazaga M, Torres C, Schwarz S. 2013. The enterococcal ABC transporter gene lsa(E) confers combined resistance to lincosamides, pleuromutilins and streptogramin A antibiotics in methicillin-susceptible and methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 68:473–475 http://dx.doi.org/10.1093/jac/dks398. [PubMed]
252. Butaye P, Devriese LA, Haesebrouck F. 2003. Antimicrobial growth promoters used in animal feed: effects of less well known antibiotics on gram-positive bacteria. Clin Microbiol Rev 16:175–188 http://dx.doi.org/10.1128/CMR.16.2.175-188.2003. [PubMed]
253. WHO. 2017. Critically important antimicrobials for human medicine. 5th revision. http://who.int/foodsafety/publications/antimicrobials-fifth/en/.
254. Schwarz S, Johnson AP. 2016. Transferable resistance to colistin: a new but old threat. J Antimicrob Chemother 71:2066–2070. [PubMed]
255. Olaitan AO, Morand S, Rolain JM. 2014. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front Microbiol 5:643 http://dx.doi.org/10.3389/fmicb.2014.00643. [PubMed]
256. Jeannot K, Bolard A, Plésiat P. 2017. Resistance to polymyxins in Gram-negative organisms. Int J Antimicrob Agents 49:526–535 http://dx.doi.org/10.1016/j.ijantimicag.2016.11.029. [PubMed]
257. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, Yu LF, Gu D, Ren H, Chen X, Lv L, He D, Zhou H, Liang Z, Liu JH, Shen J. 2016. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16:161–168 http://dx.doi.org/10.1016/S1473-3099(15)00424-7.
258. Xavier BB, Lammens C, Ruhal R, Kumar-Singh S, Butaye P, Goossens H, Malhotra-Kumar S. 2016. Identification of a novel plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016. Euro Surveill 21:pii=30280. http://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2016.21.27.30280. [PubMed]
259. Yin W, Li H, Shen Y, Liu Z, Wang S, Shen Z, Zhang R, Walsh TR, Shen J, Wang Y. 2017. Novel plasmid-mediated colistin resistance gene mcr-3 in Escherichia coli. MBio 8:e00543-17 doi:10.1128/mBio.00543-17.
260. Carattoli A, Villa L, Feudi C, Curcio L, Orsini S, Luppi A, Pezzotti G, Magistrali CF. 2017. Novel plasmid-mediated colistin resistance mcr-4 gene in Salmonella and Escherichia coli, Italy 2013, Spain and Belgium, 2015 to 2016. Euro Surveill 22:30589. http://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2017.22.31.30589. http://dx.doi.org/10.2807/1560-7917.ES.2017.22.31.30589. [PubMed]
261. Borowiak M, Fischer J, Hammerl JA, Hendriksen RS, Szabo I, Malorny B. 2017. Identification of a novel transposon-associated phosphoethanolamine transferase gene, mcr-5, conferring colistin resistance in d-tartrate fermenting Salmonella enterica subsp. enterica serovar Paratyphi B. J Antimicrob Chemother 72:3317–3324 http://dx.doi.org/10.1093/jac/dkx327. [PubMed]
262. AbuOun M, Stubberfield EJ, Duggett NA, Kirchner M, Dormer L, Nunez-Garcia J, Randall LP, Lemma F, Crook DW, Teale C, Smith RP, Anjum MF. 2017. mcr-1 and mcr-2 variant genes identified in Moraxella species isolated from pigs in Great Britain from 2014 to 2015. J Antimicrob Chemother 72:2745–2749 http://dx.doi.org/10.1093/jac/dkx286. [PubMed]
263. Ling Z, Yin W, Li H, Zhang Q, Wang X, Wang Z, Ke Y, Wang Y, Shen J. 2017. Chromosome-mediated mcr-3 variants in Aeromonas veronii from chicken meat. Antimicrob Agents Chemother 61:e01272-17. Epub ahead of print. http://dx.doi.org/10.1128/AAC.01272-17. [PubMed]
264. Eichhorn I, Feudi C, Wang Y, Kaspar H, Feßler AT, Lübke-Becker A, Michael GB, Shen J, Schwarz S. 2018. Identification of novel variants of the colistin resistance gene mcr-3 in Aeromonas spp. from the national resistance monitoring program GE RM-Vet and from diagnostic submissions. J Antimicrob Chemother. http://dx.doi.org/10.1093/jac/dkx538. [PubMed]
265. Vila-Farrés X, Ferrer-Navarro M, Callarisa AE, Martí S, Espinal P, Gupta S, Rolain JM, Giralt E, Vila J. 2015. Loss of LPS is involved in the virulence and resistance to colistin of colistin-resistant Acinetobacter nosocomialis mutants selected in vitro. J Antimicrob Chemother 70:2981–2986 http://dx.doi.org/10.1093/jac/dkv244. [PubMed]
266. Baron S, Hadjadj L, Rolain JM, Olaitan AO. 2016. Molecular mechanisms of polymyxin resistance: knowns and unknowns. Int J Antimicrob Agents 48:583–591 http://dx.doi.org/10.1016/j.ijantimicag.2016.06.023. [PubMed]
267. Bina XR, Provenzano D, Nguyen N, Bina JE. 2008. Vibrio cholerae RND family efflux systems are required for antimicrobial resistance, optimal virulence factor production, and colonization of the infant mouse small intestine. Infect Immun 76:3595–3605 http://dx.doi.org/10.1128/IAI.01620-07. [PubMed]
268. Campos MA, Vargas MA, Regueiro V, Llompart CM, Albertí S, Bengoechea JA. 2004. Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides. Infect Immun 72:7107–7114 http://dx.doi.org/10.1128/IAI.72.12.7107-7114.2004. [PubMed]
269. Llobet E, Tomás JM, Bengoechea JA. 2008. Capsule polysaccharide is a bacterial decoy for antimicrobial peptides. Microbiology 154:3877–3886 http://dx.doi.org/10.1099/mic.0.2008/022301-0. [PubMed]
270. Young ML, Bains M, Bell A, Hancock RE. 1992. Role of Pseudomonas aeruginosa outer membrane protein OprH in polymyxin and gentamicin resistance: isolation of an OprH-deficient mutant by gene replacement techniques. Antimicrob Agents Chemother 36:2566–2568 http://dx.doi.org/10.1128/AAC.36.11.2566. [PubMed]
271. Hetem DJ, Bonten MJ. 2013. Clinical relevance of mupirocin resistance in Staphylococcus aureus. J Hosp Infect 85:249–256 http://dx.doi.org/10.1016/j.jhin.2013.09.006. [PubMed]
272. Hodgson JE, Curnock SP, Dyke KG, Morris R, Sylvester DR, Gross MS. 1994. Molecular characterization of the gene encoding high-level mupirocin resistance in Staphylococcus aureus J2870. Antimicrob Agents Chemother 38:1205–1208 http://dx.doi.org/10.1128/AAC.38.5.1205. [PubMed]
273. Needham C, Rahman M, Dyke KG, Noble WC. 1994. An investigation of plasmids from Staphylococcus aureus that mediate resistance to mupirocin and tetracycline. Microbiology 140:2577–2583 http://dx.doi.org/10.1099/00221287-140-10-2577. [PubMed]
274. Poovelikunnel T, Gethin G, Humphreys H. 2015. Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA. J Antimicrob Chemother 70:2681–2692 http://dx.doi.org/10.1093/jac/dkv169. [PubMed]
275. Seah C, Alexander DC, Louie L, Simor A, Low DE, Longtin J, Melano RG. 2012. MupB, a new high-level mupirocin resistance mechanism in Staphylococcus aureus. Antimicrob Agents Chemother 56:1916–1920 http://dx.doi.org/10.1128/AAC.05325-11. [PubMed]
276. Fines M, Pronost S, Maillard K, Taouji S, Leclercq R. 2001. Characterization of mutations in the rpoB gene associated with rifampin resistance in Rhodococcus equi isolated from foals. J Clin Microbiol 39:2784–2787 http://dx.doi.org/10.1128/JCM.39.8.2784-2787.2001. [PubMed]
277. Riesenberg A, Feßler AT, Erol E, Prenger-Berninghoff E, Stamm I, Böse R, Heusinger A, Klarmann D, Werckenthin C, Schwarz S. 2014. MICs of 32 antimicrobial agents for Rhodococcus equi isolates of animal origin. J Antimicrob Chemother 69:1045–1049 http://dx.doi.org/10.1093/jac/dkt460. [PubMed]
278. Severinov K, Soushko M, Goldfarb A, Nikiforov V. 1993. Rifampicin region revisited. New rifampicin-resistant and streptolydigin-resistant mutants in the β subunit of Escherichia coli RNA polymerase. J Biol Chem 268:14820–14825. [PubMed]
279. Telenti A, Imboden P, Marchesi F, Lowrie D, Cole S, Colston MJ, Matter L, Schopfer K, Bodmer T. 1993. Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet 341:647–650 http://dx.doi.org/10.1016/0140-6736(93)90417-F.
280. Perkins AE, Nicholson WL. 2008. Uncovering new metabolic capabilities of Bacillus subtilis using phenotype profiling of rifampin-resistant rpoB mutants. J Bacteriol 190:807–814 http://dx.doi.org/10.1128/JB.00901-07. [PubMed]
281. Li J, Feßler AT, Jiang N, Fan R, Wang Y, Wu C, Shen J, Schwarz S. 2016. Molecular basis of rifampicin resistance in multiresistant porcine livestock-associated MRSA. J Antimicrob Chemother 71:3313–3315 http://dx.doi.org/10.1093/jac/dkw294. [PubMed]
282. Kadlec K, van Duijkeren E, Wagenaar JA, Schwarz S. 2011. Molecular basis of rifampicin resistance in methicillin-resistant Staphylococcus pseudintermedius isolates from dogs. J Antimicrob Chemother 66:1236–1242 http://dx.doi.org/10.1093/jac/dkr118. [PubMed]
283. Tupin A, Gualtieri M, Roquet-Banères F, Morichaud Z, Brodolin K, Leonetti JP. 2010. Resistance to rifampicin: at the crossroads between ecological, genomic and medical concerns. Int J Antimicrob Agents 35:519–523 http://dx.doi.org/10.1016/j.ijantimicag.2009.12.017. [PubMed]
284. Baysarowich J, Koteva K, Hughes DW, Ejim L, Griffiths E, Zhang K, Junop M, Wright GD. 2008. Rifamycin antibiotic resistance by ADP-ribosylation: structure and diversity of Arr. Proc Natl Acad Sci USA 105:4886–4891 http://dx.doi.org/10.1073/pnas.0711939105. [PubMed]
285. Kadlec K, von Czapiewski E, Kaspar H, Wallmann J, Michael GB, Steinacker U, Schwarz S. 2011. Molecular basis of sulfonamide and trimethoprim resistance in fish-pathogenic Aeromonas isolates. Appl Environ Microbiol 77:7147–7150 http://dx.doi.org/10.1128/AEM.00560-11. [PubMed]
286. Silver LL. 2017. Fosfomycin: mechanism and resistance. Cold Spring Harb Perspect Med 7:a025262 http://dx.doi.org/10.1101/cshperspect.a025262. [PubMed]
287. Castañeda-García A, Blázquez J, Rodríguez-Rojas A. 2013. Molecular mechanisms and clinical impact of acquired and intrinsic fosfomycin resistance. Antibiotics (Basel) 2:217–236 http://dx.doi.org/10.3390/antibiotics2020217. [PubMed]
288. Jiang Y, Shen P, Wei Z, Liu L, He F, Shi K, Wang Y, Wang H, Yu Y. 2015. Dissemination of a clone carrying a fosA3-harbouring plasmid mediates high fosfomycin resistance rate of KPC-producing Klebsiella pneumoniae in China. Int J Antimicrob Agents 45:66–70 http://dx.doi.org/10.1016/j.ijantimicag.2014.08.010. [PubMed]
289. Wachino J, Yamane K, Suzuki S, Kimura K, Arakawa Y. 2010. Prevalence of fosfomycin resistance among CTX-M-producing Escherichia coli clinical isolates in Japan and identification of novel plasmid-mediated fosfomycin-modifying enzymes. Antimicrob Agents Chemother 54:3061–3064 http://dx.doi.org/10.1128/AAC.01834-09. [PubMed]
290. Kitanaka H, Wachino J, Jin W, Yokoyama S, Sasano MA, Hori M, Yamada K, Kimura K, Arakawa Y. 2014. Novel integron-mediated fosfomycin resistance gene fosK. Antimicrob Agents Chemother 58:4978–4979 http://dx.doi.org/10.1128/AAC.03131-14. [PubMed]
291. Zilhao R, Courvalin P. 1990. Nucleotide sequence of the fosB gene conferring fosfomycin resistance in Staphylococcus epidermidis. FEMS Microbiol Lett 56:267–272. [PubMed]
292. Xu X, Chen C, Lin D, Guo Q, Hu F, Zhu D, Li G, Wang M. 2013. The fosfomycin resistance gene fosB3 is located on a transferable, extrachromosomal circular intermediate in clinical Enterococcus faecium isolates. PLoS One 8:e78106 http://dx.doi.org/10.1371/journal.pone.0078106. [PubMed]
293. Fu Z, Liu Y, Chen C, Guo Y, Ma Y, Yang Y, Hu F, Xu X, Wang M. 2016. Characterization of fosfomycin resistance gene, fosB, in methicillin-resistant Staphylococcus aureus isolates. PLoS One 11:e0154829 http://dx.doi.org/10.1371/journal.pone.0154829. [PubMed]
294. He T, Wang Y, Schwarz S, Zhao Q, Shen J, Wu C. 2014. Genetic environment of the multi-resistance gene cfr in methicillin-resistant coagulase-negative staphylococci from chickens, ducks, and pigs in China. Int J Med Microbiol 304:257–261 http://dx.doi.org/10.1016/j.ijmm.2013.10.005. [PubMed]
295. Wang Y, Yao H, Deng F, Liu D, Zhang Y, Shen Z. 2015. Identification of a novel fosX CC gene conferring fosfomycin resistance in Campylobacter. J Antimicrob Chemother 70:1261–1263. [PubMed]
296. Kim SY, Ju K-S, Metcalf WW, Evans BS, Kuzuyama T, van der Donk WA. 2012. Different biosynthetic pathways to fosfomycin in Pseudomonas syringae and Streptomyces species. Antimicrob Agents Chemother 56:4175–4183 http://dx.doi.org/10.1128/AAC.06478-11. [PubMed]
297. Biedenbach DJ, Rhomberg PR, Mendes RE, Jones RN. 2010. Spectrum of activity, mutation rates, synergistic interactions, and the effects of pH and serum proteins for fusidic acid (CEM-102). Diagn Microbiol Infect Dis 66:301–307 http://dx.doi.org/10.1016/j.diagmicrobio.2009.10.014. [PubMed]
298. Farrell DJ, Castanheira M, Chopra I. 2011. Characterization of global patterns and the genetics of fusidic acid resistance. Clin Infect Dis 52(Suppl 7) :S487–S492 http://dx.doi.org/10.1093/cid/cir164. [PubMed]
299. Lannergård J, Norström T, Hughes D. 2009. Genetic determinants of resistance to fusidic acid among clinical bacteremia isolates of Staphylococcus aureus. Antimicrob Agents Chemother 53:2059–2065 http://dx.doi.org/10.1128/AAC.00871-08. [PubMed]
300. O’Brien FG, Price C, Grubb WB, Gustafson JE. 2002. Genetic characterization of the fusidic acid and cadmium resistance determinants of Staphylococcus aureus plasmid pUB101. J Antimicrob Chemother 50:313–321 http://dx.doi.org/10.1093/jac/dkf153. [PubMed]
301. Chen HJ, Hung WC, Lin YT, Tsai JC, Chiu HC, Hsueh PR, Teng LJ. 2015. A novel fusidic acid resistance determinant, fusF, in Staphylococcus cohnii. J Antimicrob Chemother 70:416–419 http://dx.doi.org/10.1093/jac/dku408. [PubMed]
302. Baines SL, Howden BP, Heffernan H, Stinear TP, Carter GP, Seemann T, Kwong JC, Ritchie SR, Williamson DA. 2016. Rapid emergence and evolution of Staphylococcus aureus clones harboring fusC-containing Staphylococcal Cassette Chromosome elements. Antimicrob Agents Chemother 60:2359–2365 http://dx.doi.org/10.1128/AAC.03020-15. [PubMed]
303. O’Neill AJ, McLaws F, Kahlmeter G, Henriksen AS, Chopra I. 2007. Genetic basis of resistance to fusidic acid in staphylococci. Antimicrob Agents Chemother 51:1737–1740 http://dx.doi.org/10.1128/AAC.01542-06. [PubMed]
304. Werner G, Hildebrandt B, Witte W. 2001. Aminoglycoside-streptothricin resistance gene cluster aadE-sat4-aphA-3 disseminated among multiresistant isolates of Enterococcus faecium. Antimicrob Agents Chemother 45:3267–3269 http://dx.doi.org/10.1128/AAC.45.11.3267-3269.2001. [PubMed]
305. Kadlec K, Schwarz S. 2008. Analysis and distribution of class 1 and class 2 integrons and associated gene cassettes among Escherichia coli isolates from swine, horses, cats and dogs collected in the BfT-GermVet monitoring study. J Antimicrob Chemother 62:469–473 http://dx.doi.org/10.1093/jac/dkn233. [PubMed]
306. Ahmed AM, Shimamoto T. 2004. A plasmid-encoded class 1 integron carrying sat, a putative phosphoserine phosphatase gene and aadA2 from enterotoxigenic Escherichia coli O159 isolated in Japan. FEMS Microbiol Lett 235:243–248 http://dx.doi.org/10.1111/j.1574-6968.2004.tb09595.x. [PubMed]
307. Boerlin P, Burnens AP, Frey J, Kuhnert P, Nicolet J. 2001. Molecular epidemiology and genetic linkage of macrolide and aminoglycoside resistance in Staphylococcus intermedius of canine origin. Vet Microbiol 79:155–169 http://dx.doi.org/10.1016/S0378-1135(00)00347-3.
308. Kadlec K, Schwarz S, Perreten V, Andersson UG, Finn M, Greko C, Moodley A, Kania SA, Frank LA, Bemis DA, Franco A, Iurescia M, Battisti A, Duim B, Wagenaar JA, van Duijkeren E, Weese JS, Fitzgerald JR, Rossano A, Guardabassi L. 2010. Molecular analysis of methicillin-resistant Staphylococcus pseudintermedius of feline origin from different European countries and North America. J Antimicrob Chemother 65:1826–1828 http://dx.doi.org/10.1093/jac/dkq203. [PubMed]
309. Perreten V, Kadlec K, Schwarz S, Grönlund Andersson U, Finn M, Greko C, Moodley A, Kania SA, Frank LA, Bemis DA, Franco A, Iurescia M, Battisti A, Duim B, Wagenaar JA, van Duijkeren E, Weese JS, Fitzgerald JR, Rossano A, Guardabassi L. 2010. Clonal spread of methicillin-resistant Staphylococcus pseudintermedius in Europe and North America: an international multicentre study. J Antimicrob Chemother 65:1145–1154 http://dx.doi.org/10.1093/jac/dkq078. [PubMed]
310. Walther B, Monecke S, Ruscher C, Friedrich AW, Ehricht R, Slickers P, Soba A, Wleklinski CG, Wieler LH, Lübke-Becker A. 2009. Comparative molecular analysis substantiates zoonotic potential of equine methicillin-resistant Staphylococcus aureus. J Clin Microbiol 47:704–710 http://dx.doi.org/10.1128/JCM.01626-08. [PubMed]
311. Aarestrup FM. 2000. Occurrence, selection and spread of resistance to antimicrobial agents used for growth promotion for food animals in Denmark. APMIS Suppl. 101:1–8.
312. Podlesek Z, Comino A, Herzog-Velikonja B, Zgur-Bertok D, Komel R, Grabnar M. 1995. Bacillus licheniformis bacitracin-resistance ABC transporter: relationship to mammalian multidrug resistance. Mol Microbiol 16:969–976 http://dx.doi.org/10.1111/j.1365-2958.1995.tb02322.x. [PubMed]
313. Bernard R, Joseph P, Guiseppi A, Chippaux M, Denizot F. 2003. YtsCD and YwoA, two independent systems that confer bacitracin resistance to Bacillus subtilis. FEMS Microbiol Lett 228:93–97 http://dx.doi.org/10.1016/S0378-1097(03)00738-9.
314. El Ghachi M, Bouhss A, Blanot D, Mengin-Lecreulx D. 2004. The bacA gene of Escherichia coli encodes an undecaprenyl pyrophosphate phosphatase activity. J Biol Chem 279:30106–30113 http://dx.doi.org/10.1074/jbc.M401701200. [PubMed]
315. Manson JM, Keis S, Smith JM, Cook GM. 2004. Acquired bacitracin resistance in Enterococcus faecalis is mediated by an ABC transporter and a novel regulatory protein, BcrR. Antimicrob Agents Chemother 48:3743–3748 http://dx.doi.org/10.1128/AAC.48.10.3743-3748.2004.
316. Weitnauer G, Gaisser S, Trefzer A, Stockert S, Westrich L, Quiros LM, Mendez C, Salas JA, Bechthold A. 2001. An ATP-binding cassette transporter and two rRNA methyltransferases are involved in resistance to avilamycin in the producer organism Streptomyces viridochromogenes Tü57. Antimicrob Agents Chemother 45:690–695 http://dx.doi.org/10.1128/AAC.45.3.690-695.2001. [PubMed]
317. Aarestrup FM, Jensen LB. 2000. Presence of variations in ribosomal protein L16 corresponding to susceptibility of enterococci to oligosaccharides (avilamycin and evernimicin). Antimicrob Agents Chemother 44:3425–3427 http://dx.doi.org/10.1128/AAC.44.12.3425-3427.2000. [PubMed]
318. Mann PA, Xiong L, Mankin AS, Chau AS, Mendrick CA, Najarian DJ, Cramer CA, Loebenberg D, Coates E, Murgolo NJ, Aarestrup FM, Goering RV, Black TA, Hare RS, McNicholas PM. 2001. EmtA, a rRNA methyltransferase conferring high-level evernimicin resistance. Mol Microbiol 41:1349–1356 http://dx.doi.org/10.1046/j.1365-2958.2001.02602.x. [PubMed]
319. Treede I, Jakobsen L, Kirpekar F, Vester B, Weitnauer G, Bechthold A, Douthwaite S. 2003. The avilamycin resistance determinants AviRa and AviRb methylate 23S rRNA at the guanosine 2535 base and the uridine 2479 ribose. Mol Microbiol 49:309–318 http://dx.doi.org/10.1046/j.1365-2958.2003.03558.x. [PubMed]
320. Kofoed CB, Vester B. 2002. Interaction of avilamycin with ribosomes and resistance caused by mutations in 23S rRNA. Antimicrob Agents Chemother 46:3339–3342 http://dx.doi.org/10.1128/AAC.46.11.3339-3342.2002. [PubMed]
321. van den Bogaard AE, Hazen M, Hoyer M, Oostenbach P, Stobberingh EE. 2002. Effects of flavophospholipol on resistance in fecal Escherichia coli and enterococci of fattening pigs. Antimicrob Agents Chemother 46:110–118 http://dx.doi.org/10.1128/AAC.46.1.110-118.2002. [PubMed]
322. Ohmae K, Yonezawa S, Terakado N. 1981. R plasmid with carbadox resistance from Escherichia coli of porcine origin. Antimicrob Agents Chemother 19:86–90 http://dx.doi.org/10.1128/AAC.19.1.86. [PubMed]
323. Hansen LH, Johannesen E, Burmølle M, Sørensen AH, Sørensen SJ. 2004. Plasmid-encoded multidrug efflux pump conferring resistance to olaquindox in Escherichia coli. Antimicrob Agents Chemother 48:3332–3337 http://dx.doi.org/10.1128/AAC.48.9.3332-3337.2004. [PubMed]

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During the past decades resistance to virtually all antimicrobial agents has been observed in bacteria of animal origin. This chapter describes in detail the mechanisms so far encountered for the various classes of antimicrobial agents. The main mechanisms include enzymatic inactivation by either disintegration or chemical modification of antimicrobial agents, reduced intracellular accumulation by either decreased influx or increased efflux of antimicrobial agents, and modifications at the cellular target sites (i.e., mutational changes, chemical modification, protection, or even replacement of the target sites). Often several mechanisms interact to enhance bacterial resistance to antimicrobial agents. This is a completely revised version of the corresponding chapter in the book published in 2006. New sections have been added for oxazolidinones, polypeptides, mupirocin, ansamycins, fosfomycin, fusidic acid, and streptomycins, and the chapters for the remaining classes of antimicrobial agents have been completely updated to cover the advances in knowledge gained since 2006.

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Origins of antimicrobial agents

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0019-2017
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Examples of resistance to antimicrobials by (modified from ref. 8 )

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0019-2017
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Examples of resistance to antimicrobials by enzymatic inactivation

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0019-2017
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Examples of resistance to antimicrobials by (modified from ref. 8 )

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0019-2017

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