| Summary: | <i>Escherichia coli</i> O157:H7 pathogenesis is due to Shiga toxin (Stx) production, though variation in virulence has been observed. Clade 8 strains, for instance, were shown to overproduce Stx and were more common among hemolytic uremic syndrome cases. One candidate gene, <i>norV</i>, which encodes a nitric oxide (NO) reductase found in a clade 8 O157:H7 outbreak strain (TW14359), was thought to impact virulence. Hence, we screened for <i>norV</i> in 303 O157 isolates representing multiple clades, examined <i>stx2</i> expression following NO exposure in TW14359 for comparison to an isogenic mutant (Δ<i>norV</i>), and evaluated survival in THP-1 derived macrophages. <i>norV</i> was intact in strains representing clades 6–9, whereas a 204 bp deletion was found in clades 2 and 3. During anaerobic growth, NO induced <i>stx2</i> expression in TW14359. A similar increase in <i>stx2</i> expression was observed for the Δ<i>norV</i> mutant in anaerobiosis, though it was not impaired in its ability to survive within macrophages relative to TW14359. Altogether, these data suggest that NO enhances virulence by inducing Stx2 production in TW14359, and that toxin production is inhibited by NorV encoded by a gene found in most clade 8 strains. The mechanism linked to these responses, however, remains unclear and likely varies across genotypes.
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