Isoniazid induces expression of the antigen 85 complex in Mycobacterium tuberculosis

Abstract

Exposure to isoniazid induced the expression of several secreted proteins in Mycobacterium tuberculosis H37Rv. Two-dimensional gel electrophoresis and immunoblot analyses indicated that two of the prominent isonicotinic acid hydrazide-inducible polypeptides were members of the antigen 85 complex, recently demonstrated to have mycolyltransferase activity. We postulate the existence of an intermediate, whose production is inhibited by isonicotinic acid hydrazide, which plays a negative feedback regulatory role in the metabolism of mycolic acids as revealed by the overexpression of the antigen 85 complex. The approach described here relies on analyses of differential gene expression following exposure to inhibitors and may become a more general tool in dissecting the effects of antimicrobial agents.