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Quantitative Studies on the Origin and Characteristics of Streptomycin-Fast Variants of Klebsiella Pneumoniae^1,2,

From the Department of Internal Medicine of the Bowman Gray School of Medicine of Wake Forest College, Winston-Salem, N. C.

Abstract

1. Six characteristics of the streptomycin-fast variants found in an antibiotic-sensitive strain of K. pneumoniae showed striking similarity to definitive properties of gene-mutations in higher organisms. Though circumstantial in nature, such evidence strongly favors the theory proposing the existance of mutable hereditary units in bacteria which quantitatively affect the property of streptomycin-susceptibility.

2. Quantitatively, this stock strain was composed of a small number of organisms exhibiting low degrees of fastness to this antibiotic, and rare highly resistant cells in equilibrium with large numbers of sensitive organisms. The dynamics of this pattern of drug resistance appeared to be directed by factors that were inherent in each bacterial cell and its environment. When the latter was constant, the variant pattern was reproducible.

3. A strain with a high degree of fastness to streptomycin was developed in a stepwise fashion when variants with a low degree of resistance were exposed to increasing concentrations of this antibiotic. This observation was best explained by the hypothesis of successive mutation and selection. Regardless of large concentrations of streptomycin, a highly fast strain appeared in a single step if the test population included rare but very resistant variants.

4. The survival and establishment of streptomycin-fast variants at any given level of resistance appeared to be conditioned by factors concerned with the drug, the original environment, and the organism.

Footnotes

¹ This investigation was supported (in part) by a research contract from the Bacteriology Study Section, Division of Research Grants and Fellowships of the National Institute of Health, U. S. Public Health Service.

² A portion of this study was presented at the Forty-eighth General Meeting of the Society of American Bacteriologists, May 30, 1948.