ISONIAZID INDUCES EXPRESSION OF THE ANTIGEN-85 COMPLEX IN MYCOBACTERIUM-TUBERCULOSIS

Exposure to isoniazid induced the expression of several secreted prote ins in Mycobacterium tuberculosis H37Rv. Two-dimensional gel electroph oresis and immunoblot analyses indicated that two of the prominent iso nicotinic acid hydrazide-inducible polypeptides were members of the an tigen 85 complex recently demonstrated to have mycolyltransferase acti vity, We postulate the existence of an intermediate, whose production is inhibited by isonicotinic acid hydrazide, which plays a negative fe edback regulatory role in the metabolism of mycolic acids as revealed by the overexpression of the antigen 85 complex, The approach describe d here relies on analyses of differential gene expression following ex posure to inhibitors and may become a more general tool in dissecting the effects of antimicrobial agents.