The Influence of Antibiotics on the Origin of Small Colonies (G Variants), of Micrococcus Pyogenes var. Aureus1

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Abstract
In attempting to select out penicillin-resistant cultures of staphylococci from penicillin-sensitive cultures, by treatment in vitro with varying concentrations of penicillin, minute colonies (G colonies) were isolated. From 30 strains of staphylococci, G colonies were obtained under the influence of penicillin, erythromycin, carbomycin and bacitracin but not with streptomycin, oxytetracycline and chloramphenicol. Reverted large colonies were obtained from the G cultures on cultivation in the absence of antibiotics. Bacteriophage typing and comparative cultural, physiological, nutritional and virulence studies were carried out with parent, G cultures and reverted cultures. The parent and reverted strains were hemolytic, grew readily, produced coagulase, did not produce penicillinase, resisted the killing action of human blood and were virulent when injected intradermally into rabbits and intravenously into mice. The G cultures were nonhemolytic, coagulase-negative, grew slowly, possessed increased antibiotic resistance, but without penicillinase; were killed by human blood; and were avirulent for mice and rabbits. Typing with bacteriophage revealed decrease of susceptibility to bacteriophages but reversion was accompanied by return to a lytic pattern similar to that of the parent strain. Cultures of G colonies were obtained from human sources following treatment with antibacterial drugs. It is not unlikely that optimum concentrations of antibiotics for the survival of G cultures may occur in human tissues during therapy of staphylococcal infections and under these conditions avirulent small colony variants may be selected out and remain undetected. Following cessation of therapy, reversion to a virulent form may occur, and relapse of the infections may ensue.