Mechanisms involved in the resistance of Mycobacterium tuberculosis to para-aminosalicylic acid.

That para-aminobenzoic acid antagonizes competitively the inhibitory effect of paraaminosalicylic acid on the growth of Mycobacterium tuberculosis is well known. In a previous communication (Hedgecock, 1956) it was reported that inhibition of M. tuberculosis (strain H37Rv) by para-aminosalicylic acid was reversed noncompetitively by methionine and biotin when the concentration of the inhibitor did not exceed 0.5 ,ug per ml. At higher concentrations of para-aminosalicylic acid, reversal of inhibition occurred in the presence of methionine and biotin following the addition of certain fatty acids or purines as well as specified amino acids. In the present paper competitive and noncompetitive reversal of para-aminosalicylic acidinhibition was investigated in susceptible and resistant strains of M. tuberculosis which had been isolated from patients and also in resistant strains selected in vitro. Studies of the organisms were made with respect to the mechanisms involved in the development of resistance to paraaminosalicylic acid.