The influlence of antibiotics on the origin of small colonies (G( variants) of Micrococcus pyogenes var. aureiis

In attempting to select out penicillin-resistant colonies of staphylococcus from sensitive cultures by the method of Kirby (1), small G colonies were obtained. When isolated on plates of agar, the colonies in some instances appeared so minute, that growth was detected only with the aid of magnification. A study of this phenomenon was pursued further with many cultures of staphylo-coccus and with different antibiotics, and minute colonies were again isolated. The small colonies reverted to the normal larger colonies when cul-tured in the absence of antibiotics. Since the minute colonies originated under the influence of antibiotics commonly used in the therapy of staphylococcal diseases, the possibility presented itself that these colonies might also appear in pa-tients while undergoing treatment with antibiotics. This report is concerned first, with a brief sum-mary of the literature on G colonies; second, ex-periments relating to the in vitro conditions under which the minute colonies appeared with the dif-ferent antibiotics; third, changes in virulence and resistance to the antibiotics displayed by the parent colonies, small colonies, and the reverted large colonies; fourth, the sensitivity to bacterio-phage of parent colonies, G colonies and reverted colonies; and, lastly, the isolation of minute col-onies from human patients with staphylococcal disease. REVIEW OF LITERATURE Small colony variants have been described for many species of bacteria. Most of the variants reported by investigators were obtained from cul-tures submitted to unfavorable metabolic influ-ences, such as chemicals, antibiotics, and aging. In some instances, isolation was from patient