DEVELOPMENT OF INCREASED BACTERIAL RESISTANCE TO ANTIBIOTICS I

Abstract

In single colony cultures of Micrococcus pyogenes var. aureus, Streptococcus pyogenes (group A). S. agalactiae (group B), S. faecalis, Escherichia coli, and Diplococcus pneumoniae (type III), tested with penicillin, chloramphenicol, or streptomycin, the number of organisms capable of growing out to form visible colonies decreases with the concn. of the drug. The emergent colonies and subcultures of those colonies are regularly more resistant than the parent culture, and in general, their resistance is related to the concn. at which the colony had grown out. At low threshold concns. of antibiotic, 10-90 % of the organisms inoculated may survive to form colonies slightly but significantly more resistant than the parent culture. At high concns. just below the sterilizing level, only a few organisms grow out to form highly resistant colonies. Between these 2 extremes there is a smooth gradation, with no indication of discontinuous stepwise differences. A similar "spectrum" of resistance is observed in subcultures of the resistant colonies which grow out in the presence of antibiotic when they are re-tested at appropriately higher concns. of the drug. The mechanism whereby bacteria develop increased resistance to antibiotics, and the dual possibility of (a) spontaneous mutations which grow out selectively in the presence of the antibiotic, or (b) a drug-directed adaptive process, are discussed in the light of the present observations.