Two Streptomycin-resistant Variants of Meningococcus

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Abstract
Two streptomycin-resistant variants developed from each of 18 strains of meningococcus including types I, II and II alpha, when heavy seedings were planted onto a series of plates containing streptomycin in concs, varying from 40 to 10,000 y per ml. One variant, designated type A, appeared in small and approx. equal numbers on all concs. It was resistant to streptomycin in vitro and in vivo. It grew in large yellowish colonies on streptomycin-free and streptomycin-containing media. It retained the original virulence for mice possessed by its parent strain. The other variant, designated type B, appeared in greatest numbers on concs. between 100 and 400 y per ml., the concs. optimal for its multiplication. Its colonies varied in size and color depending upon the concs. of streptomycin on which they developed. They were small and gray on concs. of < 100 [gamma] per ml. and larger and slightly yellowish on concs. of 200[gamma] or more per ml. Nevertheless, the type B variants from any strain were found to be genetically identical and the differences in their colonial appearance to be detd. by the conc, of streptomycin on which they grew. The type B variants were dependent on streptomycin for multiplication in vitro and in vivo. They were non -viable on media containing concs. of < 5 [gamma] per ml. and grew best on 100-400 y per ml. They were non-virulent for mice, unless the mice received streptomycin. In mice treated with streptomycin, they produced a fatal meningococcal sepsis and were recovered from the hearts'' blood provided the cultures were made on streptomycin-containing media. Both variants retained the characteristic sugar fermentations of meningococci and the type specificity of the parent strains from which they arose. Both variants are presumed to arise from mutants which are constantly appearing in the bacterial population of the parent strain. Whether the substance required by the B variants for their multiplication is streptomycin itself or some impurity has not yet been determined. These variants developed on all of 25 prepns. of streptomycin obtained from 7 manufacturers. They failed to develop on streptomycin inactivated by hydroxylamine or by cysteine.