Supplementary Figure Legends Supplementary Figure 1 Macroscopic examination of colons and cecums of inbred strains following Citrobacter rodentium infection. Seven days after infection (morbid C3 mice), two mice from each of the inbred strains were sacrificed and their cecum and colon dissected. Although some thickening of the gut wall is visible in the B6 tissues and slightly softer fecal pellets, it is nowhere near the phenotype observed in both C3H mouse strains: the cecums appear empty and the colon is devoid of properly formed fecal pellets, thickening of the wall of the colon and haemorrhage are evident. Supplementary Figure 2 Genetic maps used for linkage analyses in the (C3 x B6)F2 cross for the survival analysis (a) and in the (C3Ou x B6)F2 cross for the survival analysis (b). These maps represent the genetic distances between adjacent markers according to the recombination fractions observed in the crosses under study. Supplementary Figure 3 Cumulative survival following Citrobacter rodentium infection in (C3 x B6)F2 mice stratified according to their genotype at both Tlr4 and Cri1. Mice were first grouped according to their genotype at Cri1 (marker 15-033125499-M) and then further stratified according to their genotype at Tlr4 (marker rs3023006). The only statistically significant differences in survival were seen between mice that inherited two copies of the B6 Cri1 allele and those inheriting at least one copy of the C3 allele at Cri1, irrespective of their Tlr4 status. “B” represents mice homozygous for the B6 allele. “C” represents mice homozygous for the C3 allele. “H” represents mice heterozygous at the typed marker. Supplementary Figure 4 Bacterial shedding in fecal pellets from infected Cri1- congenic mice. Bacterial shedding is measured as C. rodentium colony-forming units per gram of homogenized fecal matter. Six homozygous congenic mice (C3Ou.B6-Cri1) and six non-congenic littermate controls (C3Ou) were infected and transferred into bedding-free isolation cages at the specified timepoints to collect six fresh fecal pellets from each. Bacterial shedding was measured every 24-48 hours after infection. Data collection was stopped for the non-congenic strains at day 9, when signs of morbidity/mortality appeared. For the congenic mice, CFU counts were further compiled at days 14, 20 and 24 post-infection to show bacterial clearance. Mean log-transformed bacterial counts are shown in the graph and error bars depict standard deviations. Nonlinear curve fitting was performed using fourth-order polynomial functions. Supplementary Figure 5 Cumulative survival following Citrobacter rodentium infection in (C3Ou x B6)F2 mice according to their genotypes at both Cri1 and Cri2. Mice were grouped according to their genotype at the typed genetic marker most closely associated with the peak LOD score on chromosome 15 (15-039906196-M and chromosome 5 (5-116192311-M). “B” represents mice homozygous for the B6 allele. “C” represents mice homozygous for the C3H allele. “H” represents mice heterozygous at the typed marker.