{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T10:37:15Z","timestamp":1768559835116,"version":"3.49.0"},"posted":{"date-parts":[[2024,2,15]]},"group-title":"Microbiology","reference-count":83,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Candida albicans<\/jats:italic>\n                  and\n                  <jats:italic>Staphylococcus aureus<\/jats:italic>\n                  are two commonly associated pathogens that cause nosocomial infections with high morbidity and mortality. Our prior and current work using a murine model of polymicrobial intra-abdominal infection (IAI) uncovered synergistic lethality that was driven by\n                  <jats:italic>Candida<\/jats:italic>\n                  -induced upregulation of functional\n                  <jats:italic>S. aureus<\/jats:italic>\n                  \u237a-toxin leading to polymicrobial sepsis and organ damage. In order to determine the candidal effector(s) mediating enhanced virulence, an unbiased screen of\n                  <jats:italic>C. albicans<\/jats:italic>\n                  transcription factor mutants was undertaken and revealed that\n                  <jats:italic>zcf13<\/jats:italic>\n                  \u0394\/\u0394 failed to drive augmented \u237a-toxin or lethal synergism during co-infection. Using a combination of transcriptional and phenotypic profiling approaches,\n                  <jats:italic>ZCF13<\/jats:italic>\n                  was shown to regulate genes involved in pentose metabolism, including\n                  <jats:italic>RBK1<\/jats:italic>\n                  and\n                  <jats:italic>HGT7<\/jats:italic>\n                  that contribute to fungal ribose catabolism and uptake, respectively. Subsequent experiments revealed that ribose inhibited the staphylococcal\n                  <jats:italic>agr<\/jats:italic>\n                  quorum sensing system and concomitantly repressed toxicity. Unlike wild-type\n                  <jats:italic>C. albicans<\/jats:italic>\n                  ,\n                  <jats:italic>zcf13<\/jats:italic>\n                  \u0394\/\u0394 was unable to effectively utilize ribose during co-culture or co-infection leading to exogenous ribose accumulation and\n                  <jats:italic>agr<\/jats:italic>\n                  repression. Forced expression of\n                  <jats:italic>RBK1<\/jats:italic>\n                  and\n                  <jats:italic>HGT7<\/jats:italic>\n                  in the\n                  <jats:italic>zcf13<\/jats:italic>\n                  \u0394\/\u0394 mutant fully restored pathogenicity during co-infection. Collectively, our results detail the interwoven complexities of cross-kingdom interactions and highlight how intermicrobial metabolism impacts polymicrobial disease pathogenesis with devastating consequences for the host.\n                <\/jats:p>","DOI":"10.1101\/2024.02.15.580531","type":"posted-content","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T21:50:18Z","timestamp":1708033818000},"source":"Crossref","is-referenced-by-count":1,"title":["A fungal metabolic regulator underlies infectious synergism during\n                  <i>Candida albicans<\/i>\n                  -\n                  <i>Staphylococcus<\/i>\n                  aureus intra-abdominal co-infection"],"prefix":"10.64898","author":[{"given":"Saikat","family":"Paul","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia A","family":"Todd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara R","family":"Eichelberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Tkaczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bret R","family":"Sellman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mairi C","family":"Noverr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E","family":"Cassat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Paul L","family":"Fidel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian M","family":"Peters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024021908101042000_2024.02.15.580531v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00081-09"},{"key":"2024021908101042000_2024.02.15.580531v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-011-1064-7"},{"key":"2024021908101042000_2024.02.15.580531v1.3","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-009-8249-6"},{"key":"2024021908101042000_2024.02.15.580531v1.4","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000001991"},{"key":"2024021908101042000_2024.02.15.580531v1.5","first-page":"20","article-title":"Prevalence of Staphylococcus spp and Candida spp in the oral cavity and periodontal pockets of periodontal disease patients","volume":"23","year":"2010","journal-title":"Acta Odontol Latinoam"},{"key":"2024021908101042000_2024.02.15.580531v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2004.11.012"},{"key":"2024021908101042000_2024.02.15.580531v1.7","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2005.081869"},{"key":"2024021908101042000_2024.02.15.580531v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2007.06.006"},{"key":"2024021908101042000_2024.02.15.580531v1.9","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02162"},{"key":"2024021908101042000_2024.02.15.580531v1.10","doi-asserted-by":"crossref","first-page":"797550","DOI":"10.3389\/fimmu.2021.797550","article-title":"Metabolic Adaptations During Staphylococcus aureus and Candida albicans Co-Infection","volume":"12","year":"2021","journal-title":"Front Immunol"},{"key":"2024021908101042000_2024.02.15.580531v1.11","doi-asserted-by":"crossref","unstructured":"Eichelberger, K.R. , Paul, S. , Peters, B.M. & Cassat, J.E . 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