SELECTION OF MICROBIAL MUTANTS RESISTANT TO HIGH LEVELS OF pH SENSITIVE ANTIBIOTICS

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Abstract
A simple method for selection of mutants resistant to high levels of pH dependent-antibiotics is presented. This method permitted the use of a relatively small inoculum. The antibiotic actidione was inactive for Tetrahymena geleii S at pH 7, but fully active at pH 6. At pH 7, actidione in the final concn. desired and glucose were added and the sterile medium inoculated. As the pH dropped, the activity of the actidione accordingly gradually increased, resulting in a concomitant inhibition of non-resistant organisms and selection of resistant ones. It is possible by using this technic to obtain an organism resistant to high levels of the antibiotic in 3 or 4 successive transfers to higher concns. of the antibiotic, although the original incidence of resistant organisms is very low. This technic may apply to any pH sensitive antibiotic, regardless of the pH of greatest activity, and to any microorganism that changes the pH of the medium sufficiently.

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