The Inactivation of Antibacterial Agents and Their Mechanism of Action

Abstract

The reaction of certain thiol compounds with penicillin, HgCl2, pyocyanine, the antibacterial principle of Allium sativum and of Arctium minus results in the loss of antibacterial action. Cysteine, ethyl and methyl esters of cysteine, [beta] aminoethanethiol and [beta] (dimethylamino) ethanethiol all act in this manner. Homocysteine is a much less effective inactivator than cysteine, while thioglycollie acid, glutathione, [beta] thiolethanol, N-acetyl cysteine and N-(p-toluenesulfonyl) cystine are poor inactivators of penicillin. Cystine, methionine and S-methyl cysteine were, under the conditions of these expts., without visible effects on penicillin. The specificity of the inactivating agents, concentration and speed of reaction varies with the antibacterial agent used. It is postulated that a large class of antibacterial agents act by reacting with sulfhydryl groups of enzymes and that the differences in antibacterial action of various agents are dependent, among other factors, upon the ability of these agents to come into contact with the essential sulfhydryl groups.