Periplasmic superoxide dismutase protectsSalmonellafrom products of phagocyte NADPH-oxidase and nitric oxide synthase

Abstract

Superoxide dismutase (SOD) catalyzes the conversion of superoxide radical to hydrogen peroxide. Periplasmic localization of bacterial Cu,Zn-SOD has suggested a role of this enzyme in defense against extracellular phagocyte-derived reactive oxygen species. Sequence analysis of regions f lanking the Salmonella typhimurium sodC gene encoding Cu,Zn-SOD demonstrates significant homology to phage proteins, ref lecting possible bacteriophage-mediated horizontal gene transfer of this determinant among pathogenic bacteria. Salmonella deficient in Cu,Zn-SOD has reduced survival in macrophages and attenuated virulence in mice, which can be restored by abrogation of either the phagocyte respiratory burst or inducible nitric oxide synthase. Moreover, a sodC mutant is extremely susceptible to the combination of superoxide and nitric oxide. These observations suggest that SOD protects periplasmic or inner membrane targets by diverting superoxide and limiting peroxynitrite formation, and they demonstrate the ability of the respiratory burst and nitric oxide synthase to synergistically kill microbial pathogens in vivo.

Inhibition of bacterial DNA replication by zinc mobilization during nitrosative stress

“…S. enterica serovar Typhimurium ATCC 14028s or its isogenic derivatives were used and grown in media as described (7,8). S. enterica CL1000 (recA) and S. enterica CL2001 (recBC) are described in ref.…”

Defective localization of the NADPH phagocyte oxidase toSalmonella-containing phagosomes in tumor necrosis factor p55 receptor-deficient macrophages

“…Peritoneal exudate cells from WT C57BL͞6 Nramp1 G169D (ity s ), TNFR-KO Nramp1 G169D (ity s ), and TNF␣-KO Nramp1 G169D (ity s ) mice (The Jackson Laboratory) were harvested 4 days after i.p. inoculation of 1 mg͞ml sodium periodate as described (19). Peritoneal exudate cells were resuspended in RPMI medium 1640 supplemented with 10% (vol͞vol) heat-inactivated FCS (Gemini Biological Products, Calabasas, CA)͞1 mM sodium pyruvate͞10 mM Hepes͞2 mM L-glutamine (all from Sigma-Aldrich).…”

Cellular Defenses against Superoxide and Hydrogen Peroxide

“…The housekeeping E. coli enzyme and the Salmonella SodCII evidently serve to defend unidentified periplasmic targets from O 2 − that leaks from respiratory-chain components on the outer aspect of the cytoplasmic membrane (6). However, periplasmic SOD evidently plays an additional role in several bacterial pathogens, whom it helps withstand the oxidative burst of host macrophages (54) Initial surveys suggested that some obligately anaerobic bacteria lacked SOD (1)-raising the possibility that the lack of SOD was the feature that consigned them to anaerobic habitats. However, recent work has revealed that these organisms employ superoxide reductases, rather than dismutases, as scavengers (55,56).…”