REGULATION OF AN ANTIBIOTIC RESISTANCE DETERMINANT

点击翻译按钮获取中文摘要

This proposal is for research in the general area of gene control mechanisms with emphasis on the regulation of expression of a gene responsible for antibiotic resistance both in pathogenic bacteria and in the organisms that are of economic importance used to synthesize these antibiotics by fermentation. The specific system we are studing confers resistance to erythromycin and related antibiotics that inhibit bacterial protein synthesis by binding to the ribosome. In both groups of organisms, expression of resistance can be induced by the antibiotic itself, and the induced biochemical alternation involves a modification of 23S ribosomal ribonucleic acid, a structural component of the target to which the antibiotic binds. In the case of pathogenic bacteria, understanding the rules of induction permits us to predict, and hopefully avoid, forms of therapeutic failure based on the ability of MLS antibiotics to select constitutive mutants. In the case of the antibiotic-producing organisms, these same induction mechanisms appear to operate in conjunction with the commitment to antibiotic synthesis. The results obtained from the research proposed will be directly pertinent to establishing standards for the rational use of MLS antibiotics, while results from parallel studies of inducible MLS resistance in antibiotic producers suggest ways of improving antibiotic production by these organisms.