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Studies on the Mechanism of Sulfonamide Bacteriostasis, Inhibition and Resistance

Experiments with E. Coli in a Synthetic Medium

From the Thorndike Memorial Laboratory, Second and Fourth Medical Services (Harvard), Boston City Hospital, and the Department of Medicine, Harvard Medical School, Boston, Mass.

Abstract

A strain of E. coli was studied which, in a simple synthetic medium, required nicotinic acid or nicotinamide for growth from small inocula. Growth was also improved by increasing the concentration of carbon dioxide in the atmosphere.

Sulfathiazole, sulfadiazine, sulfapyridine, sulfaguanidine and sulfanilamide were bacteriostatic in relatively small concentrations, as compared with their activity against this organism in complex media.

Nicotinamide, nicotinic acid and coenzyme I did not inhibit the action of these sulfonamide drugs.

P-aminobenzoic acid is a strong inhibitor of sulfonamide action, methionine a weak inhibitor. Differences in the effect of methionine on various sulfonamide drugs may be quantitative rather than qualitative.

The development of resistance to sulfonamide action has been produced with E. coli in a simple medium. P-aminobenzoic acid prevents the development of sulfonamide resistance, while methionine delays but does not prevent the development of resistance.

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				M. LANDY, N. W. LARKUM, E. J. OSWALD, and F. STREIGHTOFF INCREASED SYNTHESIS OF p-AMINOBENZOIC ACID ASSOCIATED WITH THE DEVELOPMENT OF SULFONAMIDE RESISTANCE IN STAPHYLOCOCCUS AUREUS Science, March 19, 1943; 97(2516): 265 - 267. [Abstract] [PDF]