Susceptibilities of oxyR regulon mutants of Escherichia coli and Salmonella typhimurium to isoniazid.

Escherichia coli and Salmonella typhimurium are normally resistant to > 500 micrograms of the antituberculosis drug isonicotinic acid hydrazide (isoniazid; INH) per ml. Susceptibility to INH (< 50 micrograms/ml) has now been found for mutants that are deficient in OxyR, the oxidative stress response regulator. Two OxyR-regulated enzymes, alkyl hydroperoxide reductase and hydroperoxidase I, were identified as playing important roles in INH resistance. OxyR regulon mutants should be useful for identifying other determinants of INH resistance in both E. coli and Mycobacterium tuberculosis and for finding new INH-like drugs.