Nitrosative stress causes amino acid auxotrophy in hmp mutant Salmonella Typhimurium

Abstract

Cytotoxic nitic oxide (NO) damages various bacterial macromolecules, resulting in abnormal metabolism by mechanisms largely unknown. We show that NO can cause amino acid auxotrophy in Salmonella Typhimurium lacking major NO-metabolizing enzyme, flavohemoglobin Hmp. In NO-producing cultures, supplementation with amino acid pool restores growth of Hmp-deficient Salmonella to normal growth phases, whereas excluding Cys or BCAA Leu, Ile, or Val from amino acid pool reduces growth recovery. Data suggest that, without detoxification, NO might inactivate key enzymes in the biosynthesis pathway of amino acids essential for Salmonella replication in amino acid-limiting host environments.