Chapter 12 : The Evolution of Antibiotic Resistance

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The discovery of antibiotics in the 1930s and their development for the treatment of infectious diseases represented a major advancement for medicine. There are several distinct biochemical mechanisms such as reduced permeability, active efflux and alteration of the drug target by which antibiotic resistance can arise, and these are discussed in the chapter. Although isoniazid (isonicotinic acid hydrazide, INH) is still one of the most effective antibiotics against tuberculosis, the number of INH- and other drug-resistant strains has increased dramatically. The evolution of resistance by mutation of an endogenous gene is more the exception than the rule, since the genetic basis of most antibiotic resistance among clinically significant bacteria is horizontal transfer. Although the incidence of mutator strains in environmental microbes and their possible roles in the tailoring of antibiotic resistance genes (or any horizontally transferred determinants, such as biodegradation clusters) is difficult to examine systematically in natural populations, their importance in the evolution of resistance should not be underestimated. There are three main mechanisms of horizontal gene transfer: transduction, transformation and conjugation. Conjugative DNA transfer is the principal mechanism for the dissemination of antibiotic resistance genes. Conjugative transposons are discrete elements that are normally integrated into a bacterial genome. The common association of multiresistant integrons (MRIs) with mobile DNA elements facilitates the transit of the resistance genes that have been amassed by integrons across phylogenetic boundaries and augments the impact of integrons on bacterial evolution.

Citation: Rowe-Magnus D, Mazel D. 2006. The Evolution of Antibiotic Resistance, p 221-241. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch12
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Image of FIGURE 1

Production of antibiotics in Japan and isolation frequency of antibiotic-resistant strains. TC, tetracycline; CM, chloramphenicol; SM, streptomycin.

Citation: Rowe-Magnus D, Mazel D. 2006. The Evolution of Antibiotic Resistance, p 221-241. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch12
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Image of FIGURE 2

The cluster of antibiotic-resistant enterococci compared with related clusters identified in glycopeptide-producing actinomycetes. The numbers between the clusters indicate percent amino acid identity to the cluster.

Citation: Rowe-Magnus D, Mazel D. 2006. The Evolution of Antibiotic Resistance, p 221-241. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch12
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Image of FIGURE 3

Structural comparison of a “classical” multidrug-resistant integron and the N16961 superintegron. (Top) Schematic representation of In; the various resistance genes are associated with different sites (see text). Antibiotic resistance cassettes confer resistance to the following compounds: , aminoglycosides; , chloramphenicol; , quarternary ammonium compounds; , -lactams. The gene, which provides resistance to sulfonamides, is not a gene cassette. (Bottom) The ORFs are separated by highly homologous sequences, the VCRs.

Citation: Rowe-Magnus D, Mazel D. 2006. The Evolution of Antibiotic Resistance, p 221-241. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch12
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Biochemical mechanisms of antibiotic resistance and their genetic determinants

Citation: Rowe-Magnus D, Mazel D. 2006. The Evolution of Antibiotic Resistance, p 221-241. In Seifert H, DiRita V (ed), Evolution of Microbial Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815622.ch12

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