Regulatory and structural differences in the Cu,Zn-superoxide dismutases of Salmonella enterica and their significance for virulence.
Many of the most virulent strains of Salmonella enterica produce two distinct Cu,Zn-superoxide dismutases (SodCI and SodCII). The bacteriophage-encoded SodCI enzyme makes the greater contribution to Salmonella virulence. We have performed a detailed comparison of the functional, structural, and regulatory properties of the Salmonella SodC enzymes. Here we demonstrate that SodCI and SodCII differ with regard to specific activity, protease resistance, metal affinity, and peroxidative activity, with dimeric SodCI exhibiting superior stability and activity. In particular, monomeric SodCII is unable to retain its catalytic copper ion in the absence of zinc. We have also found that SodCI and SodCII are differentially affected by oxygen, zinc availability, and the transcriptional regulator FNR. SodCII is strongly down-regulated under anaerobic conditions and dependent on the high affinity ZnuABC zinc transport system, whereas SodCI accumulation in vitro and within macrophages is FNR-dependent. We have confirmed earlier findings that SodCII accumulation in intracellular Salmonella is negligible, whereas SodCI is strongly up-regulated in macrophages. Our observations demonstrate that differences in expression, activity, and stability help to account for the unique contribution of the bacteriophage-encoded SodCI enzyme to Salmonella virulence.
Ammendola
Serena
S
Dipartimento di Biologia, Università di Roma Tor Vergata, 00133 Rome, Italy.
Pasquali
Paolo
P
Pacello
Francesca
F
Rotilio
Giuseppe
G
Castor
Margaret
M
Libby
Stephen J
SJ
Figueroa-Bossi
Nara
N
Bossi
Lionello
L
Fang
Ferric C
FC
Battistoni
Andrea
A
D000818:Animals; D015964:Gene Expression Regulation, Bacterial; D008264:Macrophages / Q000378:metabolism; D008670:Metals / Q000737:chemistry; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008954:Models, Biological; D010100:Oxygen / Q000737:chemistry; D010447:Peptide Hydrolases / Q000378:metabolism; D012480:Salmonella Infections / Q000382:microbiology*; D019779:Salmonella enterica / Q000201:enzymology* / Q000472:pathogenicity; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000502:physiology*; D014774:Virulence; D015032:Zinc / Q000737:chemistry
D008670:Metals; D013482:Superoxide Dismutase; D010447:Peptide Hydrolases; D015032:Zinc; D010100:Oxygen