{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:57:05Z","timestamp":1791899825489,"version":"4.3.4"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>We previously found that the elevated abundance of the fungus <jats:italic>Candida tropicalis<\/jats:italic> is positively correlated with the bacteria <jats:italic>Escherichia coli<\/jats:italic> and <jats:italic>Serratia marcescens<\/jats:italic> in Crohn\u2019s disease patients and the three pathogens, when co-cultured, form a robust mixed-species biofilm. The finding suggests that these three pathogens communicate and promote biofilm formation, possibly through secretion of small signaling molecules. To identify candidate signaling molecules, we carried out a metabolomic analysis of the single-species and triple-species cultures of the three pathogens. This analysis identified 15 metabolites that were highly increased in the triple-species culture. One highly induced metabolite was indole-3-acetic acid (IAA), which has been shown to induce filamentation of certain fungi. We thus tested the effect of IAA on biofilm formation of <jats:italic>C<\/jats:italic>. <jats:italic>tropicalis<\/jats:italic> and demonstrated that IAA promotes biofilm formation of <jats:italic>C<\/jats:italic>. <jats:italic>tropicalis<\/jats:italic>. Then, we carried out isotope tracing experiments using <jats:sup>13<\/jats:sup>C-labeled-tryptophan as a precursor to uncover the biosynthesis pathway of IAA in <jats:italic>C<\/jats:italic>. <jats:italic>tropicalis<\/jats:italic>. The results indicated that <jats:italic>C<\/jats:italic>. <jats:italic>tropicalis<\/jats:italic> synthesizes IAA through the indole-3-pyruvate pathway. Further studies using inhibitors of the indole-3-pyruvate pathway are warranted to decipher the mechanisms by which IAA influences biofilm formation.<\/jats:p>","DOI":"10.1371\/journal.pone.0244246","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T20:30:13Z","timestamp":1608237013000},"page":"e0244246","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Indole-3-acetic acid synthesized through the indole-3-pyruvate pathway promotes Candida tropicalis biofilm formation"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4325-1216","authenticated-orcid":true,"given":"Masaru","family":"Miyagi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Saigusa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Umeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Saijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Hager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"McCormick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud A.","family":"Ghannoum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"pone.0244246.ref001","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.15585\/mmwr.mm6542a3","article-title":"Prevalence of inflammatory bowel disease among adults aged \u226518 years\u2014United States, 2015","volume":"65","author":"JM Dahlhamer","year":"2016","journal-title":"Morb Mortal Wkly Rep"},{"key":"pone.0244246.ref002","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1136\/gutjnl-2015-310746","article-title":"Fungal microbiota dysbiosis in IBD","volume":"66","author":"H Sokol","year":"2017","journal-title":"Gut"},{"key":"pone.0244246.ref003","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1136\/gutjnl-2013-304833","article-title":"A decrease of the butyrate-producing species roseburia hominis and faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis","volume":"63","author":"K Machiels","year":"2014","journal-title":"Gut"},{"key":"pone.0244246.ref004","doi-asserted-by":"crossref","first-page":"944","DOI":"10.3390\/nu12040944","article-title":"Nutrition, IBD and Gut Microbiota","volume":"12","author":"MM Chiara","year":"2020","journal-title":"A Review. 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