Mucispirillum schaedleri Antagonizes Salmonella Virulence to Protect Mice against Colitis

• Published in: Cell host & microbe 2019-05, Vol.25 (5), p.681-694.e8
• Main Authors: Herp, Simone, Brugiroux, Sandrine, Garzetti, Debora, Ring, Diana, Jochum, Lara M., Beutler, Markus, Eberl, Claudia, Hussain, Saib, Walter, Steffi, Gerlach, Roman G., Ruscheweyh, Hans J., Huson, Daniel, Sellin, Mikael E., Slack, Emma, Hanson, Buck, Loy, Alexander, Baines, John F., Rausch, Philipp, Basic, Marijana, Bleich, André, Berry, David, Stecher, Bärbel
• Format: Article
• Language: English
• Subjects: Agr2; altered Schaedler flora; Animals; anterior gradient protein 2 homolog; Antibiosis; ASF; Bacteria, Anaerobic - growth & development; Colitis - chemically induced; Colitis - prevention & control; colonization resistance; Disease Models, Animal; Germ-Free Life; Life Sciences; Mice; Microbiology and Parasitology; microbiome; nitrate respiration; Oligo-MM; OMM; Salmonella Infections - prevention & control; Salmonella pathogenicity island; Salmonella typhimurium - growth & development; SPI-1; T3SS; Virology
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2019.03.004

The microbiota and the gastrointestinal mucus layer play a pivotal role in protection against non-typhoidal Salmonella enterica serovar Typhimurium (S. Tm) colitis. Here, we analyzed the course of Salmonella colitis in mice lacking a functional mucus layer in the gut. Unexpectedly, in contrast to mucus-proficient littermates, genetically deficient mice were protected against Salmonella-induced gut inflammation in the streptomycin colitis model. This correlated with microbiota alterations and enrichment of the bacterial phylum Deferribacteres. Using gnotobiotic mice associated with defined bacterial consortia, we causally linked Mucispirillum schaedleri, currently the sole known representative of Deferribacteres present in the mammalian microbiota, to host protection against S. Tm colitis. Inhibition by M. schaedleri involves interference with S. Tm invasion gene expression, partly by competing for anaerobic electron acceptors. In conclusion, this study establishes M. schaedleri, a core member of the murine gut microbiota, as a key antagonist of S. Tm virulence in the gut. [Display omitted] •Mucispirillum schaedleri confers protection against Salmonella colitis in mice•Salmonella and M. schaedleri compete for anaerobic respiration substrates in the gut•M. schaedleri restricts Salmonella infection and inhibits virulence factor expression•Mucispirillum spp. are enriched in human gut mucosal samples Herp et al. find that Mucispirillum schaedleri, a low abundant member of the mammalian intestinal microbiota, metabolically competes with Salmonella enterica serovar Typhimurium, thereby interfering with virulence factor expression and subsequent tissue invasion by Salmonella. These data provide a mechanism by which members of the microbiota can antagonize invading pathogens.