ROLE OF SUPEROXIDE IN CATALASE-PEROXIDASE-MEDIATED ISONIAZID ACTION AGAINST MYCOBACTERIA

Isoniazid (INH) activation in vitro is associated with reduction of th e mycobacterial ferric KatG catalase-peroxidase by hydrazine and react ion with O-2 to form an oxyferrous enzyme complex. Since this complex could also form directly via reaction of ferric KatG with superoxide, intracellular activation might be responsive to superoxide concentrati on. When Mycobacterium smegmatis carrying the M. bovis katG gene was t reated with nontoxic levels of plumbagin, a generator of superoxide, t he bacteriostatic activity of INH increased unless a plasmid-borne sup eroxide dismutase gene,vas also present. Thus, endogenous superoxide p robably contributes to intracellular activation of INH.