The Demonstration of Naturally-occurring Streptomycin-resistant Variants in the Human Strain of Tubercle Bacillus H-37RV

Observations on Bacteria Sensitive to, Resistant to, and Dependent upon Streptomycin

“…Some differences, such as alteration in motility and changes in growth rate and in biochemical reactions, have been reported, but these have been inconsistent (Graessle and Frost, 1946;Klein and Kimmelman, 1946;Murray et al, 1946;Petroff and Lucas, 1946;Seligmann and Wassermann, 1947;Stubblefield, 1947). Streptomycin-resistant organisms have ordinarily been obtained in vitro by repeated subculture in increasing concentrations of this antibiotic (Chandler and Schoenbach, 1947;Miller and Bohnhoff, 1946;Murray et al, 1946;Price et al, 1947;Seligmann and Wassermann, 1947), though the occurrence of a few very resistant organisms in a large inoculum of sensitive ones on initial exposure to streptomycin has been described in the case of Shigella (Klein, 1947), Escherichia coli (Clark and Rantz, 1947;Klein, 1947), Staphylococcus aureus (Klein, 1947), Staphylococcus albus (Klein, 1947), Proteus vulgaris (Klein, 1947), Hemophilus influenzae (Alexander and Leidy, 1947), meningococcus (Miller and Bohnhoff, 1947a), and Mycobacterium tuberculosis (Vennesland, Ebert, and Bloch, 1947).…”

The Segregation of Streptomycin-Resistant Variants of Mycobacterium tuberculosis into Groups with Characteristic Levels of Resistance

“…tuberculosis in populations of organisms which have not previously been exposed to the antibiotic has been demonstrated in laboratory strains by Vennesland, Ebert & Bloch (1947) and Yegian & Vanderlinde (1948), and in strains obtained directly from patients by Pyle (1947). Yegian & Vanderlinde inoculated plates of a medium containing the detergent Tween 80 and streptomycin with large numbers of bacilli, and found that the number of resistant colonies that grew depended on the concentration of streptomycin.…”

Slide Culture as a Means of Appraising the Streptomycin Sensitivity of Tubercle Bacilli in Sputum

“…Pyle (1947) found no loss in the activity of streptomycin in Herrold's medium held for seven weeks at 370, but Mitchison (1950b) reported losses amounting to 90 % in the course of six weeks. Using Dubos Tween medium and assaying supernatant fluid from cultures, Vennesland, Ebert, and Bloch (1947) found losses amounting to almost 90% in four weeks at 37°. The short incubation period neededby slide cultures has therefore technical as well as clinical advantages.…”

“…Any population comprising bacteria of only a single strain may be expected to include a very large number of individuals whose sensitivities cluster closely about a modal value, together with progressively fewer organisms having sensitivities much above or much below the mode. For the tubercle bacillus, many reports testify to the existence of very infrequent individuals of very high resistance among populations drawn from strains thought to be fully sensitive to streptomycin (Pyle, 1947;Vennesland et al, 1947;Vanderlinde, 1948, 1950;Karlson and Needham, 1948;Fisher, 1948b;Yegian, Budd, and Vanderlinde, 1949;Mitchison, 1950b). This view brings resistance to drugs into line with other biological qualities of bacteria (Chick, 1930;Gardner, 1931 ;Withell, 1942;Jordan and Jacobs, 1944), and forms a link with the behaviour of other living orders (Finney, 1947).…”