Biochemical mechanisms of resistance to antimicrobial drugs

  • T. J. Franklin
  • G. A. Snow


Although the individual modes of resistance to antimicrobial drugs are very diverse, they can be grouped into a limited set of general mechanisms that account for most types of resistance encountered in medical practice. These include:
  1. 1.

    conversion of the active drug to an inactive derivative by enzyme(s) synthesized by the resistant cells;

  2. 2.
    loss of sensitivity of the drug target site as a result of:
    1. (a)

      covalent modification by enzyme activity in the resistant cells

    2. (b)

      mutation(s) affecting the target, or

    3. (c)

      acquisition of genetic information encoding either a drug-resistant form of the target enzyme or overproduction of the drug-sensitive enzyme.

  3. 3.

    Removal of the drug from the cellular interior by drug efflux systems located in the cell envelope.



Clavulanic Acid Drug Efflux Chloramphenicol Acetyl 1411 Transferase Drug Efflux Pump Acetyl Coenzyme 
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Further reading

  1. Arthur, M., Reynolds, P. and Courvalin, P. (1996). Glycopeptide resistance in enterococci. Trends Microbiol. 4, 401.PubMedCrossRefGoogle Scholar
  2. Bennett, P. M. and Chopra, I. (1993). Molecular basis of ß-lactamase induction in bacteria. Antimicrob. Agents Chemother. 37, 153.PubMedCrossRefGoogle Scholar
  3. Borst, P. and Ouellette, M. (1995). New mechanisms of drug resistance in parasitic protozoa. Ann. Rev. Microbiol. 49, 427.CrossRefGoogle Scholar
  4. Bush, K., Jacoby, G. A. and Medeiros, A. A. (1995). A functional classification scheme for 3-lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother. 39, 1211.PubMedCrossRefGoogle Scholar
  5. Chopra, I. et al. (1997). The search for antimicrobial agents effective against bacteria resistant to multiple antibiotics. Antimicrob. Agents Chemother. 41, 497.PubMedGoogle Scholar
  6. Cole, S. T. (1994). Mycobacterium tuberculosis: drug resistance mechanisms. Trends Microbiol. 2, 411.Google Scholar
  7. Davies, J. (1994). Inactivation of antibiotics and the dis- semination of resistance genes. Science 264, 375.PubMedCrossRefGoogle Scholar
  8. Ghuysen, J.-M. et al. (1996). Pencillin and beyond: evolution, protein fold, multimodular polypeptides and multidomain complexes. Microb. Drug Resist. 2, 163.PubMedCrossRefGoogle Scholar
  9. Huovinen, P. et al. (1995). Trimethoprim and sulfonamide resistance. Antimicrob. Agents Chemother. 39, 279.PubMedCrossRefGoogle Scholar
  10. Katz, R. A. and Skalka, A. M. (1994). The retroviral enzymes. Ann. Rev. Biochem. 63, 133.PubMedCrossRefGoogle Scholar
  11. Livermore, D. M. (1995). Bacterial resistance to carbapenems. In Antimicrobial Resistance: A Crisis in Health Care (eds D. J. Jungkind et al.), Plenum Press, New York, p. 35.Google Scholar
  12. Molla, A. et al. (1996). Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nature Medicine 2, 760.PubMedCrossRefGoogle Scholar
  13. Murray, I. A. and Shaw, W. V. (1997). 0-acetyl transferases for chloramphenicol and other natural products. Antimicrob. Agents Chemother. 41, 1.Google Scholar
  14. Park, J. T. (1996). The convergence of murein recycling research with 3-lactamase research. Microb. Drug Resist. 2, 105.PubMedCrossRefGoogle Scholar
  15. Paulsen, I. T., Brown, M. H. and Skurray, R. A. (1996). Proton-dependent multidrug efflux systems. Microbiol. Rev. 60, 575.PubMedGoogle Scholar
  16. Payne, D. J. (1993). Metallo-ß-lactamases — a new therapeutic challenge. J. Med. Microbiol. 39, 93.PubMedCrossRefGoogle Scholar
  17. Richman, D. (1994). Drug resistance in viruses. Trends Microbiol. 2, 401.PubMedCrossRefGoogle Scholar
  18. Roberts, M. C. (1996). Tetracycline resistance determinants; mechanisms of action, regulation of expression, genetic mobility and distribution. FEMS Microbiol. Rev. 19, 1.PubMedCrossRefGoogle Scholar
  19. Sanglard, D. et al. (1995). Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob. Agents Chemother. 39, 2378.PubMedCrossRefGoogle Scholar
  20. Shaw, K. J. et al. (1993). Molecular genetics of amino-glycoside resistance genes and familial relationships of aminoglycoside-modifying enzymes. Microbiol. Rev. 57, 138.PubMedGoogle Scholar
  21. Spratt, B. G. (1994). Resistance to antibiotics mediated by target alterations. Science 264, 388.PubMedCrossRefGoogle Scholar
  22. Su, X.-Z. et al. (1997). Complex polymorphisms in a —330 kDa protein are linked to chloroquine-resistant R falciparum in Southeast Asia and Africa. Cell 91, 593.PubMedCrossRefGoogle Scholar
  23. Thanassi, D. G., Suh, G. S. B. and Nikaido, H. (1995). Role of outer membrane in efflux-mediated tetracycline resistance of Escherichia coli. J. Bacteriol. 177, 998.Google Scholar
  24. Van den Bossche, H., Marichal, P. and Odds, F. C. (1994) Molecular mechanisms of drug resistance in fungi. Trends Microbiol. 2, 393.CrossRefGoogle Scholar
  25. Weisblum, B. V. (1995). Erythromycin resistance by ribosome modification. Antimicrob. Agents Chemother. 39, 577.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1998

Authors and Affiliations

  • T. J. Franklin
    • 1
  • G. A. Snow
    • 1
  1. 1.Zeneca PharmaceuticalsMacclesfield, CheshireUK

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