Glucose 6-phosphate dehydrogenase is required for Salmonella typhimurium virulence and resistance to reactive oxygen and nitrogen intermediates

Salmonella typhimurium zwf mutants lacking glucose 6-phosphate dehydrogenas e (G6PD) activity have increased susceptibility to reactive oxygen and nitr ogen intermediates as well as attenuated virulence in mice. Abrogation of t he phagocyte respiratory burst oxidase during experimental infection with z wf mutant Salmonella causes a prompt restoration of virulence, while inhibi tion of inducible nitric oxide synthase results in delayed lethality. These observations suggest that G6PD-dependent bacterial antioxidant defenses pl ay an important pathogenic role during early salmonellosis and additionally may help to antagonize NO-dependent antimicrobial mechanisms later in the course of infection.