Zinc-dependent substrate-level phosphorylation powers Salmonella growth under nitrosative stress of the innate host response
Fig 3
Salmonella require znuB to recover from nitrosative stress and cause disease.
(A) Growth of wild-type (WT) and ΔznuB Salmonella after challenge with 5 mM diethylenetriamine (DETA) or 5 mM DETA NONOate (dNO) in E salts minimal media supplemented with glucose (EG), casamino acids (ECA), or glucose and casaminmo acids (EGCA). Where indicated, media were supplemented with 5 μM ZnCl2 (+ZnCl2) (N = 5 to 10, mean). (B) Intracellular growth of WT and ΔznuB Salmonella after 20 h of culture in J774 macrophage-like cells. Select samples were treated with 500 μM of the iNOS inhibitor aminoguanidine (AG) (N = 16, mean ± S.E.M.). (C) Intracellular survival of Salmonella in periodate-elicited macrophages from C57BL/6 or iNOS-/- mice (N = 5, mean ± S.D.) * and ***, p < 0.05 and <0.001, respectively, as determined by two-way ANOVA. (D) Survival of C57BL/6 or iNOS deficient (iNOS-/-) mice infected i.p. with approximately 100 CFU of wild-type (WT) or ΔznuB Salmonella (N = 7–9 mice). p < 0.0001 and 0.001 for C57BL/6 and iNOS-/-, respectively, as determined by logrank analysis.