Abstract
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.
conversion of the active drug to an inactive derivative by enzyme(s) synthesized by the resistant cells;
-
2.
loss of sensitivity of the drug target site as a result of:
-
(a)
covalent modification by enzyme activity in the resistant cells,
-
(b)
mutation(s) affecting the target, or
-
(c)
acquisition of genetic information encoding either a drug-resistant form of the target enzyme or overproduction of the drug-sensitive enzyme.
-
(a)
-
3.
Removal of the drug from the cellular interior by drug efflux systems located in the cell envelope.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Further reading
Arthur, M., Reynolds, P. and Courvalin, P (1996). Glycopeptide resistance in enterococci. Trends Microbiol. 4, 401.
Bennett, P M. and Chopra, 1. (1993). Molecular basis of ß-lactamase induction in bacteria. Antimicrob. Agents Chemother. 37, 153.
Borst, P and Ouellette, M. (1995). New mechanisms of drug resistance in parasitic protozoa. Ann. Rev. Microbiol. 49, 427.
Bush, K., Jacoby, G. A. and Medeiros, A. A. (1995). A functional classification scheme for ß-lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother. 39, 1211.
Chopra, I. et al. (1997). The search for antimicrobial agents effective against bacteria resistant to multiple antibiotics. Antimicrob. Agents Chemother. 41, 497.
Cole, S. T. (1994). Mycobacterium tuberculosis: drug resistance mechanisms. Trends Microbiol. 2, 411.
Davies, J. (1994). Inactivation of antibiotics and the dissemination of resistance genes. Science 264, 375.
Ghuysen, J.-M. et al. (1996). Pencillin and beyond: evolution, protein fold, multimodular polypeptides and multidomain complexes. Microb. Drug Resist. 2, 163.
Huovinen, P. et al. (1995). Trimethoprim and sulfonamide resistance. Antimicrob. Agents Chemother. 39, 279.
Katz, R. A. and Skalka, A. M. (1994). The retroviral enzymes. Ann. Rev. Biochem. 63, 133.
Livermore, D. M. (1995). Bacterial resistance to car- bapenems. In Antimicrobial Resistance: A Crisis in Health Care (eds D. J. Jungkind et al.), Plenum Press, New York, p.35.
Molla, A. et al. (1996). Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nature Medicine 2, 760.
Murray, I. A. and Shaw, W V (1997). O-acetyl transferases for chloramphenicol and other natural products. Antimicrob. Agents Chemother. 41,1.
Park, J. T. (1996). The convergence of murein recycling research with ß-lactamase research. Microb. Drug Resist. 2, 105.
Paulsen, I. T, Brown, M. H. and Skurray, R. A. (1996). Proton-dependent multidrug efflux systems. Microbiol. Rev. 60, 575.
Payne, D. J. (1993). Metallo-ß-lactamases — a new therapeutic challenge. J. Med. Microbiol. 39, 93.
Richman, D. (1994). Drug resistance in viruses. Trends Microbiol. 2,401.
Roberts, M. C. (1996). Tetracycline resistance determinants; mechanisms of action, regulation of expression, genetic mobility and distribution. FEMS Microbiol. Rev. 19, 1.
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.
Shaw, K. J. et al. (1993). Molecular genetics of aminoglycoside resistance genes and familial relationships of aminoglycoside-modifying enzymes. Microbiol. Rev. 57, 138.
Spratt, B. G. (1994). Resistance to antibiotics mediated by target alterations. Science 264, 388.
Su, X.-Z. et al. (1997). Complex polymorphisms in a —330 kDa protein are linked to chloroquine-resist- ant R falciparum in Southeast Asia and Africa. Cell 91, 593.
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.
Van den Bossche, H., Marichal, P and Odds, F. C. (1994) Molecular mechanisms of drug resistance in fungi. Trends Microbiol. 2, 393.
Weisblum, B. V (1995). Erythromycin resistance by ribo- some modification. Antimicrob. Agents Chemother. 39, 577.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 1998 The Kluwer Academic Publishers
About this chapter
Cite this chapter
Franklin, T.J., Snow, G.A. (1998). Biochemical mechanisms of resistance to antimicrobial drugs. In: Biochemistry and Molecular Biology of Antimicrobial Drug Action. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-9127-5_9
Download citation
DOI: https://doi.org/10.1007/978-94-010-9127-5_9
Publisher Name: Springer, Dordrecht
Print ISBN: 978-0-412-82190-5
Online ISBN: 978-94-010-9127-5
eBook Packages: Springer Book Archive