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Inducible Resistance to Macrolides, Lincosamides, and Streptogramin Type-B Antibiotics: The Resistance Phenotype, Its Biological Diversity, and Structural Elements That Regulate Expression

Bernard Weisblum


Reports of erythromycin-resistant strains of Staphylococcus aureus began to appear in the clinical literature in the mid-1950s, shortly after the introduction of this drug into clinical practice (Chabbert 1956; Jones et al. 1956; Garrod 1957). The mechanism of resistance in these clinical isolates can be ascribed to reduced affinity between erythromycin and its binding site on the 50S subunit of the ribosome (Saito et al. 1969; Weisblum et al. 1971), which in turn results from a specific structural modification of the ribosome (Lai and Weisblum 1971; Lai et al. 1973a,b; Saito and Mitsuhashi 1980). The structural modification, methylation of adenine in 23S ribosomal RNA (rRNA), confers resistance to three chemically distinct groups of antibiotics that inhibit 50S ribosome subunit function: the macrolides, lincosamides, and Streptogramin type-B (MLS) antibiotics. The material presented in this paper has been organized under the headings of three genera (namely Stapphylococcus, Streptococcus, and Streptomyces), which illustrate the biological diversity of MLS resistance, the more general form of clinical erythromycin resistance, with emphasis on the variations of inducer and induced phenotype that occur in these organisms, followed by a discussion of the structure and function of genetic control elements, studied in model systems, which regulate expression of this interesting resistance mechanism at the molecular level.

Historical Background
Early reports of erythromycin-resistant S. aureus noted that such strains were either coresistant to other macrolides or that they could rapidly become so (Chabbert 1956; Jones et al. 1956; Garrod 1957). It was also...

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