Self-protection mechanisms in antibiotic producers.

Various ways in which antibiotic-producing organisms are able to resist the actions of their products are discussed. Examples are given of antibiotic inactivation and also the modification of antibiotic target sites (most notably, ribosomes) to which drugs would otherwise bind and thereby exert their usual inhibitory effects. An interesting variation on the latter theme involves the duplication of target enzymes so that both sensitive and resistant versions are produced, the latter inducibly. Speculative discussion of antibiotic efflux leads to examples of cloned resistance determinants that probably encode components of efflux systems. Although of interest in their own right, resistance mechanisms should not be viewed narrowly when the physiology of antibiotic producers is considered. Thus, chemical modification of drug molecules may not only fulfil a protective role within the cell but may also provide substrates for efflux. Recent evidence that such considerations apply to macrolide antibiotics is presented. The control of resistance in producing organisms is also discussed with particular reference to the induction of novobiocin resistance in Streptomyces sphaeroides. This involves the interplay of novobiocin-sensitive and -resistant forms of DNA gyrase and features a promoter that displays a dramatic response to changes in DNA topology.