Erythromycin-Inducible Resistance in Staphylococcus aureus: Requirements for Induction

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Abstract
At least two functionally different types of ribosomes are found in strains of Staphylococcus aureus which display "dissociated" resistance to erythromycin. One type of ribosome is found under conditions of growth in ordinary nutrient broth, and the second is formed during growth in the presence of erythromycin. In these strains, erythromycin acts as an inducer of resistance to three different classes of inhibitors of the 50S ribosomal subunit-the macrolides, lincosamides, and streptogramin B-type antibiotics. The optimal inducing concentration of erythromycin is between 10(-8) and 10(-7)m. Concentrations as low as 10(-9)m can produce a 10-fold increase in resistant cells over the uninduced, background level, whereas concentrations greater than 10(-7)m block induction owing to inhibition of protein synthesis. Resistant cells begin to appear within 5 to 10 min after addition of erythromycin (to 10(-7)m), and within 40 min (i.e., about one generation) more than 90% of the entire culture is resistant to erythromycin as well as to lincomycin and vernamycin B(alpha). A resistant culture becomes sensitive if grown for 90 min in the absence of erythromycin. The process of induction is inhibited by chloramphenicol and streptovaricin, which inhibit protein and ribonucleic acid synthesis, respectively, but not by novobiocin, which inhibits deoxyribonucleic acid synthesis. Resistant cells produced in this manner fail to concentrate (14)C-erythromycin and (14)C-lincomycin, but not (14)C-chloramphenicol. Constitutively erythromycin-resistant strains which do not require the presence of erythromycin for expression of resistance can be selected on media containing antibiotics which belong to any one of the three classes. Two patterns of constitutive resistance have been found. These are (i) generalized constitutive resistance-which involves resistance in the absence of erythromycin to all members of each of the three cited classes of 50S subunit inhibitors which were tested, and (ii) partial constitutive resistance-which involves different degrees of resistance, in the absence of erythromycin, to various members of the three classes. Several different patterns of variable constitutivity are possible. 50S ribosomal subunits isolated from induced or constitutively resistant cells show decreased ability to bind erythromycin and lincomycin, and possible enzymatic inactivation of these antibiotics has been rigorously excluded. The induced change, therefore involves modification of ribosome structure rather than modification of the antibiotic.

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