{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T18:50:50Z","timestamp":1776019850580,"version":"3.50.1"},"posted":{"date-parts":[[2024,8,8]]},"group-title":"Microbiology","reference-count":130,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,8,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Enteric pathogens engage in complex interactions with the host and the resident microbiota to establish gut colonization. Although mechanistic interactions between enteric pathogens and bacterial commensals have been extensively studied, whether and how commensal fungi affect pathogenesis of enteric infections remains largely unknown. Here we show that colonization with the common human gut commensal fungus\n                  <jats:italic>Candida albicans<\/jats:italic>\n                  worsened infections with the enteric pathogen\n                  <jats:italic>Salmonella enterica<\/jats:italic>\n                  serovar Typhimurium. Presence of\n                  <jats:italic>C. albicans<\/jats:italic>\n                  in the mouse gut increased\n                  <jats:italic>Salmonella<\/jats:italic>\n                  cecum colonization and systemic dissemination. We investigated the underlying mechanism and found that\n                  <jats:italic>Salmonella<\/jats:italic>\n                  binds to\n                  <jats:italic>C. albicans<\/jats:italic>\n                  via Type 1 fimbriae and uses its Type 3 Secretion System (T3SS) to deliver effector proteins into\n                  <jats:italic>C. albicans<\/jats:italic>\n                  . A specific effector, SopB, was sufficient to manipulate\n                  <jats:italic>C. albicans<\/jats:italic>\n                  metabolism, triggering increased arginine biosynthesis in\n                  <jats:italic>C. albicans<\/jats:italic>\n                  and the release of millimolar amounts of arginine into the extracellular environment. The released arginine, in turn, induced T3SS expression in\n                  <jats:italic>Salmonella<\/jats:italic>\n                  , increasing its invasion of epithelial cells.\n                  <jats:italic>C. albicans<\/jats:italic>\n                  deficient in arginine production was unable to increase\n                  <jats:italic>Salmonella<\/jats:italic>\n                  virulence\n                  <jats:italic>in vitro<\/jats:italic>\n                  or\n                  <jats:italic>in vivo<\/jats:italic>\n                  . In addition to modulating pathogen invasion, arginine also directly influenced the host response to infection. Arginine-producing\n                  <jats:italic>C. albicans<\/jats:italic>\n                  dampened the inflammatory response during\n                  <jats:italic>Salmonella<\/jats:italic>\n                  infection, whereas\n                  <jats:italic>C. albicans<\/jats:italic>\n                  deficient in arginine production did not. Arginine supplementation in the absence of\n                  <jats:italic>C. albicans<\/jats:italic>\n                  increased the systemic spread of\n                  <jats:italic>Salmonella<\/jats:italic>\n                  and decreased the inflammatory response, phenocopying the presence of\n                  <jats:italic>C. albicans<\/jats:italic>\n                  . In summary, we identified\n                  <jats:italic>C. albicans<\/jats:italic>\n                  colonization as a susceptibility factor for disseminated\n                  <jats:italic>Salmonella<\/jats:italic>\n                  infection, and arginine as a central metabolite in the cross-kingdom interaction between fungi, bacteria, and host.\n                <\/jats:p>","DOI":"10.1101\/2024.08.08.606421","type":"posted-content","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T23:50:19Z","timestamp":1723161019000},"source":"Crossref","is-referenced-by-count":5,"title":["Commensal Yeast Promotes\n                  <i>Salmonella<\/i>\n                  Typhimurium Virulence"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0681-3956","authenticated-orcid":false,"given":"Kanchan","family":"Jaswal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1092-1984","authenticated-orcid":false,"given":"Olivia A","family":"Todd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto C","family":"Flores Audelo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5940-3769","authenticated-orcid":false,"given":"William","family":"Santus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saikat","family":"Paul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manmeet","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Underhill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-2077","authenticated-orcid":false,"given":"Brian M","family":"Peters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0109-1090","authenticated-orcid":false,"given":"Judith","family":"Behnsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024081003051057000_2024.08.08.606421v1.1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.752295"},{"key":"2024081003051057000_2024.08.08.606421v1.2","doi-asserted-by":"crossref","unstructured":"Rogers, A. 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