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Selection of Bacterial Mutants of Increased Sensitivity to ‘Aminopterin’

Abstract

SOME understanding of the cellular responses which modify the effectiveness of growth-inhibitors can be gained by the study of closely related populations of microbial or mammalian cells differing in degree of sensitivity to a drug. Microbial cell lines resistant to antibiotics and antimetabolites can be developed readily by the selection of cells capable of surviving in the presence of increasing concentrations of such drugs1. Similar selection of drug-resistant neoplastic cells has been accomplished both in vivo 2 and in vitro 3. Occasionally the development of resistance to one drug is accompanied by changes which confer an increased sensitivity to a different agent, a finding applicable to both microbial4 and neoplastic cells2,5. The physiological mechanisms and metabolic systems associated with any increased effectiveness of drugs are of vital concern, but have received little attention because of the technical difficulty of directing the selection towards an increased, rather than decreased, responsiveness to a drug if that drug is used as the selecting agent. This communication concerns the reproducible selection in the absence of the drug of bacterial mutants of increased sensitivity to a folic acid antagonist (‘Aminopterin’).

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NICHOL, C. Selection of Bacterial Mutants of Increased Sensitivity to ‘Aminopterin’. Nature 183, 550–551 (1959). https://doi.org/10.1038/183550a0

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