NAD Metabolism In Salmonella typhimurium: Isolation of Pyridine Analogue Supersensitive (pas) and pas Suppressor Mutants

Abstract

Mutants of S. typhimurium supersensitive to the nicotinic acid analog 6-aminonicotinic acid (6ANA) were isolated as unable to grow on what are normally subinhibitory concentrations of the analog. The mutations were classified on the basis of their map positions as pasA (89-92 units), pasB (66-69 units), pasC (18-22 units), pasD (18 units) and pasE (55 units). The mutants exhibited a wide range of minimal inhibitory concentrations towards 6ANA, and several were affected in terms of growth. Evidently, most of the mutations probably reside in genes whose products utilize NAD as a cofactor, the altered gene products being more sensitive to internal 6-amino NAD concentrations. Secondary mutations which suppress the Pas- phenotype were found to reside in the folling NAD-related loci; pncB, nadB and nadD. Two of the pncB mutants appear to be affected in the expression of nicotinic acid phosphoribosyltransferase while several of the nadB mutants are apparently insensitive to feedback inhibition by internal NAD concentrations.