The specific resistance of tubercle bacilli to para-aminosalicylic acid and sulfonamides

The observation by Youmans et al. (1947) that para-aminobenzoic acid (PABA) antagonizes the action of para-aminosalicylic acid (PAS) has been confirmed repeatedly. Since the role of PABA has come to assume such a cen-tral position in explaining the mechanism and site of action of the sulfonamides, the question now arises, Do PAS and the sulfonamides inhibit the same meta-bolic process? The development of resistant strains of microorganisms provides a means of investigating this problem. If we assume that the two drugs act at similar sites, then an independently developed strain resistant to sulfonamides should, a priori, be resistant to PAS and a PAS-resistant strain should likewise be resist-ant to the sulfonamides. Experiment 1. The development of a strain of Mycobacterium tuberculosis, H37Rv, highly resistant to PAS was accomplished by serial transfer through liquid sorbitan monooleate medium containing increasing concentrations of the drug. The resistant mutant grew well at a concentration of 500 uAg of PAS pe