Bacterial strains and plasmids used are listed in Supplementary Table 1. S. Typhimurium was routinely cultured in LB broth or on LB agar plates. Construction of tetrathionate respiration deficient mutants is described in the Supplementary Methods. Tetrathionate broth (BD Biosciences) or mucin broth (0.05 % hog mucin [Sigma-Aldrich] in minimal media supplemented with 40 mM sodium tetrathionate as indicated) was inoculated with 100 colony forming units(CFU) /ml of each strain and incubated at 37°C for 16 h either with aeration, statically or anaerobically as indicated. All animal experiments were approved by the Institutional Animal Care and Use Committees at the University of California, Davis (mouse experiments) or the Texas A&M University (calf experiments). Ligated ileal loop surgery was performed as described previously 17 (link). A S. Typhimurium mouse colitis model has been described 14 (link). Groups of 10-12 week old, female mice (C57BL/6, B6.129S-Cybbtm1Din/J, B6.129P2-Nos2tm1Lau/J; The Jackson Laboratory) were orally infected with S. Typhimurium and tissue samples collected 4 days later. Bacterial numbers were determined by spreading serial 10-fold dilutions of tissue homogenates on selective media. The competitive index was calculated by dividing the number of wild-type cells by the number of mutant cells and normalized by the input ratio. Formalin fixed, Hematoxylin and Eosin (H&E) stained cecal sections were examined for signs of inflammation (Supplementary Figure 2). Tetrathionate concentration of cecal extracts was measured by RP-LC-MS. To measure relative expression levels of Kc and Nos2 mRNA, total RNA was isolated from the cecum using TRI reagent (Molecular Research Center), reverse transcribed (TaqMan reverse transcription reagents; Applied Biosystems) and SYBR-Green (Applied Biosystems) based real-time PCR performed using the primers listed in Supplementary Table 2. Fold changes in mRNA levels measured by real-time PCR, tetrathionate concentrations, and bacterial numbers underwent logarithmic transformation before ANOVA analysis followed by Student’s t-test.