Resistance to antibiotics in antibiotic-producing streptomyces.
thesisposted on 19.11.2015, 09:07 by Richard Henry. Skinner
Mechanisms by which antibiotic-producing streptomycetes are specifically resistant to their products have been investigated. Two radically different mechanisms were encountered. Firstly, Streptomyces vinaceus and Streptomyces capreolus appear to be resistant to their products, viomycin and capreomycin, respectively, through the possession of novel enzymes (viomycin/capreomycin phosphotransferase, capreomycin acetyltransferase) which have the capacity to maintain intracellular antibiotic in inactive forms. The sites of modification by these enzymes have been established with varying degrees of certainty. The ribosomes of these organisms are just as sensitive to these antibiotics as are those of non-producing bacteria. The gene encoding viomycin phosphotransferase has been cloned from S. vinaceus into Streptomyces lividans, in which it determines resistance to viomycin. In contrast, the resistance of the erythromycin-producing organism, Streptomyces erythreus. to its product results from the total insensitivity of its ribosomes to the antibiotic. This insensitivity was shown to be due to a specific dimethylation of a single adenosine residue in 23S ribosomal RNA and the enzyme responsible for this modification was isolated and purified. This RNA methylation also renders ribosomes resistant to other antibiotics (members of the MLS group) which share a common ribosomal binding-site with erythromycin. These results validate a previous hypothesis that the mechanism of resistance in the erythromycin-producing organism is essentially identical with that previously found in erythromycin-resistant clinical strains of bacteria. The possible evolutionary relationship of the methylases from the two different sources is discussed, as are the potential applications of such enzymes to the study of ribosome structure and function.