1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Mechanisms of Antibiotic Resistance

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Buy this Microbiology Spectrum Article
Price Non-Member $15.00
  • Authors: Jose M. Munita1, Cesar A. Arias4
  • Editors: Indira T. Kudva7, Qijing Zhang8
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical School at Houston, Houston, TX 77030; 2: International Center for Microbial Genomics; 3: Clinica Alemana de Santiago, Universidad del Desarrollo School of Medicine, Santiago, Chile; 4: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical School at Houston, Houston, TX 77030; 5: International Center for Microbial Genomics; 6: Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia; 7: National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA; 8: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA
  • Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0016-2015
  • Received 20 April 2015 Accepted 27 July 2015 Published 08 April 2016
  • Cesar A. Arias, cesar.arias@uth.tmc.edu
image of Mechanisms of Antibiotic Resistance
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Mechanisms of Antibiotic Resistance, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/4/2/VMBF-0016-2015-1.gif /docserver/preview/fulltext/microbiolspec/4/2/VMBF-0016-2015-2.gif
  • Abstract:

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens.

  • Citation: Munita J, Arias C. 2016. Mechanisms of Antibiotic Resistance. Microbiol Spectrum 4(2):VMBF-0016-2015. doi:10.1128/microbiolspec.VMBF-0016-2015.

References

1. World Health Organization. 2014. Antimicrobial Resistance: Global Report on Surveillance 2014. WHO, Geneva Switzerland. http://www.who.int/drugresistance/documents/surveillancereport/en/.
2. Cosgrove SE. 2006. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis 42(Suppl 2):S82–S89. [PubMed][CrossRef]
3. DiazGranados CA, Zimmer SM, Klein M, Jernigan JA. 2005. Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis 41:327–333. [PubMed][CrossRef]
4. Sydnor ER, Perl TM. 2011. Hospital epidemiology and infection control in acute-care settings. Clin Microbiol Rev 24:141–173. [PubMed][CrossRef]
5. Centers for Disease Control and Prevention. 2013. Antibiotic Resistance Threats in the United States. Centers for Disease Control and Prevention, 2013. CDC, Atlanta, GA. http://www.cdc.gov/drugresistance/threat-report-2013/index.html.
6. The Review on Antimicrobial Resistance. 2014. Antimicrobial Resistance: Tackling a Crisis for the Future Health and Wealth of Nations. http://amr-review.org.
7. Clinical and Laboratory Standards Institute. 2014. Performance Standards for Antimicrobial Susceptibility Testing; 24th informational supplement. CLSI document M100-S24. CLSI, Wayne, PA.
8. Nannini EC, Singh KV, Arias CA, Murray BE. 2013. In vivo effect of cefazolin, daptomycin, and nafcillin in experimental endocarditis with a methicillin-susceptible Staphylococcus aureus strain showing an inoculum effect against cefazolin. Antimicrob Agents Chemother 57:4276–4281. [PubMed][CrossRef]
9. Manson JM, Hancock LE, Gilmore MS. 2010. Mechanism of chromosomal transfer of Enterococcus faecalis pathogenicity island, capsule, antimicrobial resistance, and other traits. Proc Natl Acad Sci USA 107:12269–12274. [PubMed][CrossRef]
10. Thomas CM, Nielsen KM. 2005. Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nat Rev Microbiol 3:711–721. [PubMed][CrossRef]
11. Wilson DN. 2014. Ribosome-targeting antibiotics and mechanisms of bacterial resistance. Nat Rev Microbiol 12:35–48. [PubMed][CrossRef]
12. Ramirez MS, Tolmasky ME. 2010. Aminoglycoside modifying enzymes. Drug Resist Updat 13:151–171. [PubMed][CrossRef]
13. Hollenbeck BL, Rice LB. 2012. Intrinsic and acquired resistance mechanisms in enterococcus. Virulence 3:421–433. [PubMed][CrossRef]
14. Schwarz S, Kehrenberg C, Doublet B, Cloeckaert A. 2004. Molecular basis of bacterial resistance to chloramphenicol and florfenicol. FEMS Microbiol Rev 28:519–542. [PubMed][CrossRef]
15. Abraham EP, Chain E. 1940. An enzyme from bacteria able to destroy penicillin. Nature 146:837. [CrossRef]
16. D’Costa VM, King CE, Kalan L, Morar M, Sung WW, Schwarz C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB, Poinar HN, Wright GD. 2011. Antibiotic resistance is ancient. Nature 477:457–461. [PubMed][CrossRef]
17. Bush K. 2013. Proliferation and significance of clinically relevant β-lactamases. Ann N Y Acad Sci 1277:84–90. [PubMed][CrossRef]
18. Paterson DL, Bonomo RA. 2005. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev 18:657–686. [PubMed][CrossRef]
19. Bush K. 2013. The ABCD’s of β-lactamase nomenclature. J Infect Chemother 19:549–559. [PubMed][CrossRef]
20. Bush K, Jacoby GA. 2010. Updated functional classification of β-lactamases. Antimicrob Agents Chemother 54:969–976. [PubMed][CrossRef]
21. Sirot D, Sirot J, Labia R, Morand A, Courvalin P, Darfeuille-Michaud A, Perroux R, Cluzel R. 1987. Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: identification of CTX-1, a novel beta-lactamase. J Antimicrob Chemother 20:323–334. [PubMed][CrossRef]
22. Bonnet R. 2004. Growing group of extended-spectrum beta lactamases: the CTX-M enzymes. Antimicrob Agents Chemother 48:1–14. [PubMed][CrossRef]
23. Poirel L, Lartigue M-F, Decousser J-W, Nordmann P. 2005. ISEcp1B-mediated transposition of blaCTX-M in Escherichia coli. Antimicrob Agents Chemother 49:447–450. [PubMed][CrossRef]
24. Queenan AM, Bush K. 2007. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 20:440–458. [PubMed][CrossRef]
25. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, Alberti S, Bush K, Tenover FC. 2001. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 45:1151–1161. [PubMed][CrossRef]
26. Nordmann P, Cuzon G, Naas T. 2009. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 9:228–236. [PubMed][CrossRef]
27. Poirel L, Pitout JD, Nordmann P. 2007. Carbapenemases: molecular diversity and clinical consequences. Future Microbiol 2:501–512. [PubMed][CrossRef]
28. Cornaglia G, Giamarellou H, Rossolini GM. 2011. Metallo-β-lactamases: a last frontier for β-lactams? Lancet Infect Dis 11:381–393. [PubMed][CrossRef]
29. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, Chaudhary U, Doumith M, Giske CG, Irfan S, Krishnan P, Kumar AV, Maharjan S, Mushtaq S, Noorie T, Paterson DL, Pearson A, Perry C, Pike R, Rao B, Ray U, Sarma JB, Sharma M, Sheridan E, Thirunarayan MA, Turton J, Upadhyay S, Warner M, Welfare W, Livermore DM, Woodford N. 2010. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 10:597–602. [PubMed][CrossRef]
30. Nordmann P, Poirel L, Walsh TR, Livermore DM. 2011. The emerging NDM carbapenemases. Trends Microbiol 19:588–595. [PubMed][CrossRef]
31. Walsh TR, Weeks J, Livermore DM, Toleman MA. 2011. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study. Lancet Infect Dis 11:355–362. [PubMed][CrossRef]
32. Jacoby GA. 2009. AmpC beta-lactamases. Clin Microbiol Rev 22:161–182. [PubMed][CrossRef]
33. Jacobs C, Frère JM, Normark S. 1997. Cytosolic intermediates for cell wall biosynthesis and degradation control inducible beta-lactam resistance in Gram-negative bacteria. Cell 88:823–832. [PubMed][CrossRef]
34. Johnson JW, Fisher JF, Mobashery S. 2013. Bacterial cell wall recycling. Ann N Y Acad Sci 1277:54–75. [PubMed][CrossRef]
35. Schmidtke AJ, Hanson ND. 2006. Model system to evaluate the effect of ampD mutations on AmpC-mediated beta-lactam resistance. Antimicrob Agents Chemother 50:2030–2037. [PubMed][CrossRef]
36. Evans BA, Amyes SG. 2014. OXA β-lactamases. Clin Microbiol Rev 27:241–263. [PubMed][CrossRef]
37. Pagès JM, James CE, Winterhalter M. 2008. The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat Rev Microbiol 6:893–903. [PubMed][CrossRef]
38. Hancock RE, Brinkman FS. 2002. Function of pseudomonas porins in uptake and efflux. Annu Rev Microbiol 56:17–38. [PubMed][CrossRef]
39. Nikaido H. 2003. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67:593–656. [PubMed][CrossRef]
40. Quinn JP, Dudek EJ, DiVincenzo CA, Lucks DA, Lerner SA. 1986. Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections. J Infect Dis 154:289–294. [PubMed][CrossRef]
41. Hasdemir UO, Chevalier J, Nordmann P, Pagès J-M. 2004. Detection and prevalence of active drug efflux mechanism in various multidrug resistant Klebsiella pneumoniae strains from Turkey. J Clin Microbiol 42:2701–2706. [PubMed][CrossRef]
42. Doménech-Sánchez A, Martínez-Martínez L, Hernández-Allés S, del Carmen Conejo M, Pascual A, Tomás JM, Albertí S, Benedí VJ. 2003. Role of Klebsiella pneumoniae OmpK35 porin in antimicrobial resistance. Antimicrob Agents Chemother 47:3332–3335. [PubMed][CrossRef]
43. McMurry LM, Petrucci RE, Jr, Levy SB. 1980. Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli. Proc Natl Acad Sci USA 77:3974–3977. [PubMed][CrossRef]
44. Poole K. 2005. Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 56:20–51. [PubMed][CrossRef]
45. Singh KV, Weinstock GM, Murray BE. 2002. An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this species to clindamycin and quinupristin–dalfopristin. Antimicrob Agents Chemother 46:1845–18450. [PubMed][CrossRef]
46. Piddock LJ. 2006. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin Microbiol Rev 19:382–402. [PubMed][CrossRef]
47. Roberts MC. 2005. Update on acquired tetracycline resistance genes. FEMS Microbiol Lett 245:195–203. [PubMed][CrossRef]
48. Visalli MA, Murphy E, Projan SJ, Bradford PA. 2003. AcrAB multidrug efflux pump is associated with reduced levels of susceptibility to tigecycline (GAR-936) in Proteus mirabilis. Antimicrob Agents Chemother 47:665–669. [PubMed][CrossRef]
49. Dean CR, Visalli MA, Projan SJ, Sum PE, Bradford PA. 2003. Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1. Antimicrob Agents Chemother 47:972–978. [PubMed][CrossRef]
50. 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. [PubMed][CrossRef]
51. Connell SR, Tracz DM, Nierhaus KH, Taylor DE. 2003. Ribosomal protection proteins and their mechanism of tetracycline resistance. Antimicrob Agents Chemother 47:3675–3681. [PubMed][CrossRef]
52. Dönhöfer A, Franckenberg S, Wickles S, Berninghausen O, Beckmann R, Wilson DN. 2012. Structural basis for TetM-mediated tetracycline resistance. Proc Natl Acad Sci USA 109:16900–16905. [PubMed][CrossRef]
53. Li W, Atkinson GC, Thakor NS, Allas U, Lu CC, Chan KY, Tenson T, Schulten K, Wilson KS, Hauryliuk V, Frank J. 2013. Mechanism of tetracycline resistance by ribosomal protection protein Tet(O). Nat Commun 4:1477. [PubMed][CrossRef]
54. Martinez-Martinez L, Pascual A, Jacoby GA. 1998. Quinolone resistance from a transferable plasmid. Lancet 351:797–799. [PubMed][CrossRef]
55. Rodríguez-Martínez JM, Cano ME, Velasco C, Martínez-Martínez L, Pascual A. 2011. Plasmid-mediated quinolone resistance: an update. J Infect Chemother 17:149–12. [PubMed][CrossRef]
56. Aldred KJ, Kerns RJ, Osheroff N. 2014. Mechanism of quinolone action and resistance. Biochemistry 53:1565–1574. [PubMed][CrossRef]
57. Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, Darst SA. 2001. Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 104:901–912. [PubMed][CrossRef]
58. Floss HG, Yu TW. 2005. Rifamycin: mode of action, resistance, and biosynthesis. Chem Rev 105:621–632. [PubMed][CrossRef]
59. Hooper DC. 2002. Fluoroquinolone resistance among Gram-positive cocci. Lancet Infect Dis 2:530–538. [PubMed][CrossRef]
60. Mendes RE, Deshpande LM, Jones RN. 2014. Linezolid update: stable in vitro activity following more than a decade of clinical use and summary of associated resistance mechanisms. Drug Resist Updat 17:1–12. [PubMed][CrossRef]
61. 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 46:3334–3336. [PubMed][CrossRef]
62. Leclercq R. 2002. Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications. Clin Infect Dis 34:482–492. [PubMed][CrossRef]
63. Weisblum B. 1995. Erythromycin resistance by ribosome modification. Antimicrob Agents Chemother 39:577–585. [PubMed][CrossRef]
64. Roberts MC. 2008. Update on macrolide-lincosamide-streptogramin, ketolide, and oxazolidinone resistance genes. FEMS Microbiol Lett 282:147–159. [PubMed][CrossRef]
65. Katz L, Ashley GW. 2005. Translation and protein synthesis: macrolides. Chem Rev 105:499–528. [PubMed][CrossRef]
66. Toh SM, Xiong L, Arias CA, Villegas MV, Lolans K, Quinn J, Mankin AS. 2007. Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid. Mol Microbiol 64:1506–1514. [PubMed][CrossRef]
67. Locke JB, Zurenko GE, Shaw KJ, Bartizal K. 2014. Tedizolid for the management of human infections: in vitro characteristics. Clin Infect Dis 58(Suppl 1):S35–S42. [PubMed][CrossRef]
68. Hiramatsu K, Ito T, Tsubakishita S, Sasaki T, Takeuchi F, Morimoto Y, Katayama Y, Matsuo M, Kuwahara-Arai K, Hishinuma T, Baba T. 2013. Genomic basis for methicillin resistance in Staphylococcus aureus. Infect Chemother 45:117. [PubMed][CrossRef]
69. Moellering RC. 2012. MRSA: the first half century. J Antimicrob Chemother 67:4–11. [PubMed][CrossRef]
70. Chambers HF, Deleo FR. 2009. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 7:629–641. [PubMed][CrossRef]
71. Chambers HF. 1997. Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications. Clin Microbiol Rev 10:781–791. [PubMed]
72. Reynolds PE. 1989. Structure, biochemistry and mechanism of action of glycopeptide antibiotics. Eur J Clin Microbiol Infect Dis 8:943–950. [PubMed][CrossRef]
73. Arias CA, Murray BE. 2012. The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol 10:266–278. [PubMed][CrossRef]
74. Miller WR, Munita JM, Arias CA. 2014. Mechanisms of antibiotic resistance in enterococci. Expert Rev Anti Infect Ther 12:1221–1236. [PubMed][CrossRef]
75. Guardabassi L, Agersø Y. 2006. Genes homologous to glycopeptide resistance vanA are widespread in soil microbial communities. FEMS Microbiol Lett 259:221–225. [PubMed][CrossRef]
76. Courvalin P. 2006. Vancomycin resistance in Gram-positive cocci. Clin Infect Dis 42:S25–S34. [PubMed][CrossRef]
77. Arthur M. 2010. Antibiotics: vancomycin sensing. Nat Chem Biol 6:313–315. [PubMed][CrossRef]
78. Arthur M, Molinas C, Courvalin P. 1992. The VanS-VanR two-component regulatory system controls synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J Bacteriol 174:2582–2591. [PubMed]
79. Sievert DM, Rudrik JT, Patel JB, McDonald LC, Wilkins MJ, Hageman JC. Vancomycin-resistant Staphylococcus aureus in the United States, 2002-2006. Clin Infect Dis 46:668–674. [PubMed][CrossRef]
80. Rossi F, Diaz L, Wollam A, Panesso D, Zhou Y, Rincon S, Narechania A, Xing G, Di Gioia TS, Doi A, Tran TT, Reyes J, Munita JM, Carvajal LP, Hernandez-Roldan A, Brandão D, van der Heijden IM, Murray BE, Planet PJ, Weinstock GM, Arias CA. 2014. Transferable vancomycin resistance in a community-associated MRSA lineage. N Engl J Med 370:1524–1531. [PubMed][CrossRef]
81. Van Bambeke F, Chauvel M, Reynolds PE, Fraimow HS, Courvalin P. 1999. Vancomycin-dependent Enterococcus faecalis clinical isolates and revertant mutants. Antimicrob Agents Chemother 43:41–47. [PubMed]
82. Flensburg J, Sköld O. 1987. Massive overproduction of dihydrofolate reductase in bacteria as a response to the use of trimethoprim. Eur J Biochem 162:473–476. [PubMed][CrossRef]
83. Huovinen P. 2001. Resistance to trimethoprim sulfamethoxazole. Clin Infect Dis 32:1608–1614. [PubMed][CrossRef]
84. Hamilton-Miller JM. 1988. Reversal of activity of trimethoprim against Gram-positive cocci by thymidine, thymine and ‘folates.’ J Antimicrob Chemother 22:35–39. [PubMed][CrossRef]
85. Zervos MJ, Schaberg DR. 1985. Reversal of the in vitro susceptibility of enterococci to trimethoprim–sulfamethoxazole by folinic acid. Antimicrob Agents Chemother 28:446–448. [PubMed][CrossRef]
86. Pogliano J, Pogliano N, Silverman JA. 2012. Daptomycin-mediated reorganization of membrane architecture causes mislocalization of essential cell division proteins. J Bacteriol 194:4494–4504. [PubMed][CrossRef]
87. Zhang T, Muraih JK, Tishbi N, Herskowitz J, Victor RL, Silverman J, Uwumarenogie S, Taylor SD, Palmer M, Mintzer E. 2014. Cardiolipin prevents membrane translocation and permeabilization by daptomycin. J Biol Chem 289:11584–11591. [PubMed][CrossRef]
88. Arias CA, Panesso D, McGrath DM, Qin X, Mojica MF, Miller C, Diaz L, Tran TT, Rincon S, Barbu EM, Reyes J, Roh JH, Lobos E, Sodergren E, 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 365:892–900. [PubMed][CrossRef]
89. Munita JM, Tran TT, Diaz L, Panesso D, Reyes J, Murray BE, Arias CA. 2013. A liaF codon deletion abolishes daptomycin bactericidal activity against vancomycin-resistant Enterococcus faecalis. Antimicrob Agents Chemother 57:2831–2833. [PubMed][CrossRef]
90. Diaz L, Tran TT, Munita JM, Miller WR, Rincon S, Carvajal LP, Wollam A, Reyes J, Panesso D, Rojas NL, Shamoo Y, Murray BE, Weinstock GM, Arias CA. 2014. Whole-genome analyses of Enterococcus faecium isolates with diverse daptomycin MICs. Antimicrob Agents Chemother 58:4527–4534. [PubMed][CrossRef]
91. Munita JM, Panesso D, Diaz L, Tran TT, Reyes J, Wanger A, Murray BE, Arias CA. 2012. Correlation between mutations in liaFSR of Enterococcus faecium and MIC of daptomycin: revisiting daptomycin breakpoints. Antimicrob Agents Chemother 56:4354–4359. [PubMed][CrossRef]
92. Munita JM, Mishra NN, Alvarez D, Tran TT, Diaz L, Panesso D, Reyes J, Murray BE, Adachi JA, Bayer AS, Arias CA. 2014. Failure of high-dose daptomycin for bacteremia caused by daptomycin-susceptible Enterococcus faecium harboring LiaSR substitutions. Clin Infect Dis 59:1277–1280. [PubMed][CrossRef]
93. Wolf D, Kalamorz F, Wecke T, Juszczak A, Mäder U, Homuth G, Jordan S, Kirstein J, Hoppert M, Voigt B, Hecker M, Mascher T. 2010. In-depth profiling of the LiaR response of Bacillus subtilis. J Bacteriol 192:4680–4693. [PubMed][CrossRef]
94. Tran TT, Panesso D, Mishra NN, Mileykovskaya E, Guan Z, Munita JM, Reyes J, Diaz L, Weinstock GM, Murray BE, Shamoo Y, Dowhan W, Bayer AS, Arias CA. 2013. Daptomycin-resistant Enterococcus faecalis diverts the antibiotic molecule from the division septum and remodels cell membrane phospholipids. MBio 4(4):e00281-13. doi:10.1128/mBio.00281-13. [CrossRef]
95. Reyes J, Panesso D, Tran TT, Mishra NN, Cruz MR, Munita JM, Singh KV, Yeaman MR, Murray BE, Shamoo Y, Garsin D, Bayer AS, Arias CA. 2014. A liaR deletion restores susceptibility to daptomycin and antimicrobial peptides in multidrug-resistant Enterococcus faecalis. J Infect Dis. [Epub ahead of print.] doi:10.1093/infdis/jiu602. [CrossRef]
96. 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 analysis of a daptomycin-susceptible Enterococcus faecium strain and its daptomycin-resistant variant arising during therapy. Antimicrob Agents Chemother 57:261–268. [PubMed][CrossRef]
97. Bayer AS, Schneider T, Sahl HG. 2013. Mechanisms of daptomycin resistance in Staphylococcus aureus: role of the cell membrane and cell wall. Ann N Y Acad Sci 1277:139–158. [PubMed][CrossRef]
98. Krute CN, Carroll RK, Rivera FE, Weiss A, Young RM, Shilling A, Botlani M, Varma S, Baker BJ, Shaw LN. 2015. The disruption of prenylation leads to pleiotropic rearrangements in cellular behavior in Staphylococcus aureus. Mol Microbiol 95:819–832. [PubMed][CrossRef]
99. Ernst CM, Kuhn S, Slavetinsky CJ, Krismer B, Heilbronner S, Gekeler C, Kraus D, Wagner S, Peschel A. 2015. The lipid-modifying multiple peptide resistance factor is an oligomer consisting of distinct interacting synthase and flippase subunits. MBio 6(1):e02340-14. doi:10.1128/mBio.02340-14. [CrossRef]
100. Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 40:135–136. [PubMed][CrossRef]
101. Howden BP, Davies JK, Johnson PD, Stinear TP, Grayson ML. 2010. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin Microbiol Rev 23:99–139. [PubMed][CrossRef]
102. Stryjewski ME, Corey GR. 2014. Methicillin-resistant Staphylococcus aureus: an evolving pathogen. Clin Infect Dis 58(Suppl 1):S10–S19. [PubMed][CrossRef]
103. Bae IG, Federspiel JJ, Miró JM, Woods CW, Park L, Rybak MJ, Rude TH, Bradley S, Bukovski S, de la Maria CG, Kanj SS, Korman TM, Marco F, Murdoch DR, Plesiat P, Rodriguez-Creixems M, Reinbott P, Steed L, Tattevin P, Tripodi MF, Newton KL, Corey GR, Fowler VG, Jr, International Collaboration on Endocarditis-Microbiology Investigator. 2009. Heterogeneous vancomycin-intermediate susceptibility phenotype in bloodstream methicillin-resistant Staphylococcus aureus isolates from an international cohort of patients with infective endocarditis: prevalence, genotype, and clinical significance. J Infect Dis 200:1355–1366. [PubMed][CrossRef]
104. Gardete S, Tomasz A. 2014. Mechanisms of vancomycin resistance in Staphylococcus aureus. J Clin Invest 124:2836–2840. [PubMed][CrossRef]
105. Watanabe Y, Cui L, Katayama Y, Kozue K, Hiramatsu K. 2011. Impact of rpoB mutations on reduced vancomycin susceptibility in Staphylococcus aureus. J Clin Microbiol 49:2680–2684. [PubMed][CrossRef]
106. Jana S, Debb JK. 2006. Molecular understanding of aminoglycoside action and resistance. Appl Microbiol Biotechnol 70:140–150. [PubMed][CrossRef]
107. Piddock LJ. 2006. Multidrug-resistance efflux pumps: not just for resistance. Nat Rev Microbiol 4:629–636. [PubMed][CrossRef]
108. Du D, van Veen HW, Luisi BF. 2015. Assembly and operation of bacterial tripartite multidrug efflux pumps. Trends Microbiol 23:311–319. [PubMed][CrossRef]
109. Du D, Wang Z, James NR, Voss JE, Klimont E, Ohene-Agyei T, Venter H, Chiu W, Luisi BF. 2014. Structure of the AcrAB-TolC multidrug efflux pump. Nature 509:512–515. [PubMed][CrossRef]
110. Hobbs EC, Yin X, Paul BJ, Astarita JL, Storz G. 2014. Conserved small protein associates with the multidrug efflux pump AcrB and differentially affects antibiotic resistance. Proc Natl Acad Sci USA 109:16696–16701. [PubMed][CrossRef]
microbiolspec.VMBF-0016-2015.citations
cm/4/2
content/journal/microbiolspec/10.1128/microbiolspec.VMBF-0016-2015
Loading

Citations loading...

Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.VMBF-0016-2015
2016-04-08
2017-05-24

Abstract:

Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Representation of different types of aminoglycoside-modifying enzymes and their nomenclature. Each group of enzymes is identified by their biochemical activity as follows: acetyltransferase (AAC), adenyltransferase (ANT), and phosphotransferase (APH). Next in the enzyme name, an algebraic number in parentheses indicates the number of the carbon that is inactivated. The ring of the sugar in which the reaction takes place is symbolized by one (first sugar moiety) or two apostrophes (second sugar moiety). Roman numerals are used to differentiate distinct isoenzymes acting in the same site. Not all existing enzymes are shown. A, amikacin; G, gentamicin; I, isepamicin; K, kanamycin; N, netilmicin; S, sisomicin; T, tobramycin. Modified from reference 106 .

Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0016-2015
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Schematic representation of β-lactamases. Molecular classification of β-lactamases follows the Ambler classification. Correlation with the main functional group of the Bush and Jacobi classification is also shown. Of note, the latter classification has several subgroups that are not shown. Representative examples of each group of enzymes are provided. Class A enzymes are the most diverse and include penicillinases, ESBLs, and carbapenemases. Ambler class D enzymes belong to the functional group/subgroup 2d. *Class A enzymes belonging to the subgroup 2br are resistant to clavulanic acid inhibition. EDTA, ethylenediaminetetraacetic acid; ESBLs, extended-spectrum β-lactamases.

Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0016-2015
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

Representation of different types of efflux pumps in Gram-positive and Gram-negative bacteria. The five major families of efflux pumps are shown: ATP-binding cassette (ABC) superfamily, the major facilitator superfamily (MFS), the multidrug and toxic-compound extrusion (MATE) family, the small multidrug resistance (SMR) family, and the resistance nodulation division (RND) family. A diagrammatic comparison of all the families showing their source of energy and examples of drugs and compounds that serve as a substrate are shown. Modified from reference 107 with permission.

Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0016-2015
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4
FIGURE 4

Schematic representation of the mechanism of action and resistance to linezolid. Linezolid interferes with the positioning of aminoacyl-tRNA by interactions with the peptidyl-transferase center (PTC). Ribosomal proteins L3 and L4 associated with resistance are shown. Representation of domain V of 23S rRNA showing mutations associated with linezolid resistance. Position A2503, which is the target of Cfr methylation, is highlighted. Adapted from reference 92 .

Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0016-2015
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5
FIGURE 5

Schematic representation of the posttranscriptional control of the gene. Under noninducing conditions, the ErmC leader peptide is produced and the mRNA forms two hairpins, preventing the ribosome from recognizing the ribosomal binding site (RBS) of . As a result, translation is inhibited. After exposure to erythromycin (EM, yellow star), the antibiotic interacts with the ribosome and binds tightly to the leader peptide, stalling progression of translation. This phenomenon releases the RBS and permits translation. RBS, ribosomal binding site of the leader; RBS, ribosomal binding site of ; AUG, initiation codon. Ribosome represented in blue and erythromycin in yellow.

Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0016-2015
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 6
FIGURE 6

Schematic representation of peptidoglycan biosynthesis and mechanisms of vancomycin action and resistance . Normal peptidoglycan production. Binding of the antibiotic to the terminal -Ala--Ala of the peptidoglycan precursors prevents transpeptidation and transglycosylation, interrupting cell wall synthesis and resulting in bacterial death. The change in peptidoglycan synthesis produced by the expression of the gene cluster. Change of the terminal dipeptide from -Ala--Ala to -Ala--Lac markedly reduces the binding of vancomycin to the peptidoglycan target permitting cell wall synthesis to continue.

Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0016-2015
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 7
FIGURE 7

Diagrammatic representation of the mechanism of action of daptomycin. DAP, daptomycin; PG, phosphatidylglycerol; CM, cell membrane.

Source: microbiolspec April 2016 vol. 4 no. 2 doi:10.1128/microbiolspec.VMBF-0016-2015
Permissions and Reprints Request Permissions
Download as Powerpoint

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error