Contribution and Interaction of Shiga Toxin Genes to O157:H7 Virulence.

O157:H7 is the predominant cause of diarrhea-associated hemolytic uremic syndrome (HUS) worldwide. Its cardinal virulence traits are Shiga toxins, which are encoded by genes, the most common of which are , , and The toxins these genes encode differ in their in vitro and experimental phenotypes, but the human population-level impact of these differences is poorly understood. Using Shiga toxin-encoding bacteriophage insertion typing and real-time polymerase chain reaction, we genotyped isolates from 936 O157:H7 cases and verified HUS status via chart review. We compared the HUS risk between isolates with and those with and another gene and estimated additive interaction of the genes. Adjusted for age and symptoms, the HUS incidence of O157:H7 containing alone was 4.4% greater (95% confidence interval (CI) -0.3%, 9.1%) than when it occurred with . When and occur together, the risk of HUS was 27.1% lower (95% CI -87.8%, -2.3%) than would be expected if interaction were not present. At the population level, temporal or geographic shifts toward these genotypes should be monitored, and genotype may be an important consideration in clinically predicting HUS among O157:H7 cases.