Inhibition of Methionine Synthesis in Escherichia coli by 2-Chloro-4-Aminobenzoic Acid and Sulfanilamide.

The bacteriostatic action of 2-chloro-4-aminobenzoic acid (2-Cl-PAB) was found by Wyss, Rubin, and Strandskov (1943) to be completely reversed by p-aminobenzoic acid. This, according to the theory of Woods (1940) that p-aminobenzoic acid is a specific antagonist for sulfanilamide, classified the bacteriostatic action of 2-Cl-PAB as sulfonamide activity. The bacteriostatic action of this compound did, however, differ from that of the sulfonamides in that it could be completely reversed by methionine. The action of the sulfonamides is only partially reversed by this amino acid. Shive and Roberts (1946) hav-e suggested that the sulfonamides interfere wvith a number of enzyme systems in which p-aminobenzoic acid functions and that the enzyme system which is most sensitive to the sulfonamides is the one responsible for the synthesis of methionine. Because the bacteriostatic action of 2-Cl-PAB is completely revTersed by methionine, they postulate that 2-Cl-PAB inhibits only the enzyme system involved in the synthesis of this amino acid. The work reported here is a study of the inhibition of methionine synthesis bv 2-Cl-PAB and sulfanilamide. Strains of Escherichia coli made resistant to 2-Cl-PAB and a strain made resistant to sulfanilamide were employed. The mechanism of the development of resistance to 2-Cl-PAB was also investigated.