Interference of azide with cysteine biosynthesis in Salmonella typhimurium.

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