THE MULTIPLE MECHANISMS OF PENICILLIN RESISTANCE

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Abstract
Some strains of bacteria produce an extracellular penicillinase which converts penicillin to penicilloic acid, which is not bactericidal and is not selectively bound by penicillin-sensitive bacteria. Some resistant strains of Micro-coccus pyogenes are actually penicillin dependent. These 2 mechanisms account for the resistance of only a limited number of bacterial strains. Experiments using isotopically labeled penicillin indicate at least 3 additional mechanisms of penicillin resistance. Escherichia coli Proteus morganii, and Shigella paradvsenteriae. among others, do not liberate penicillinase into the medium, but rapidly degrade penicillin after it enters the cell. The most important single determinant of penicillin resistance in bacteria as they occur in nature may be their varying combining affinity with the antibiotic. Among bacteria which do not degrade penicillin, resistant strains regularly bind less penicillin under standard conditions than do sensitive strains; and cell-free extracts also bind penicillin in relation to the sensitivity of the intact cell. The overall combining affinity of the cell may parallel the reactivity of vital cellular components which are inactivated by their combination with the antibiotic. Penicillin-resistant variants of normally sensitive cells may combine with penicillin to the same degree as the parent sensitive cell without being killed as the result of that combination. The mechanisms of resistance in such resistant variants are as yet unknown.

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