Interference of Azide with Cysteine Biosynthesis in Salmonella typhimurium

Abstract

The growth inhibition of S. typhimurium aziA mutants by NaN3 is reversed by cystine and related compounds. NADPH-sulfite reductase (H2Se:NADP+ oxidoreductase; EC 1.8.1.2), an enzyme of cysteine biosynthesis, is inhibited in cell extracts by NaN3. AziB mutants which are able to grow in the presence of the inhibitor without cystine were isolated. About half were mapped in the cysK gene and have only residual activity of its product, O-acetylserine sulfhydrylase A [O-acetyl-L-serine acetate-lyase (adding H2S); EC 4.2.99.8]. Sensitivity of wild type and aziA mutants to NaN3 was also reversed by a constitutive mutation in cysB, the regulatory gene of cysteine biosynthesis. CysK and cysB mutants showed cross-resistance to NaN3 and 1,2,4-triazole. The resistance of these mutants to NaN3 may be due to an increased activity of NADPH-sulfite reductase.