{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:53:33Z","timestamp":1790780013168,"version":"4.1.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2013,4,9]],"date-time":"2013-04-09T00:00:00Z","timestamp":1365465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Biofilm formation by\n            <jats:named-content content-type=\"genus-species\">Candida albicans<\/jats:named-content>\n            on medically implanted devices poses a significant clinical challenge. Here, we compared biofilm-associated gene expression in two clinical\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            isolates, SC5314 and WO-1, to identify shared gene regulatory responses that may be functionally relevant. Among the 62 genes most highly expressed in biofilms relative to planktonic (suspension-grown) cells, we were able to recover insertion mutations in 25 genes. Twenty mutants had altered biofilm-related properties, including cell substrate adherence, cell-cell signaling, and azole susceptibility. We focused on one of the most highly upregulated genes in our biofilm proles,\n            <jats:italic>RHR2<\/jats:italic>\n            , which specifies the glycerol biosynthetic enzyme glycerol-3-phosphatase. Glycerol is 5-fold-more abundant in biofilm cells than in planktonic cells, and an\n            <jats:italic>rhr2<\/jats:italic>\n            \u0394\/\u0394 strain accumulates 2-fold-less biofilm glycerol than does the wild type. Under\n            <jats:italic>in vitro<\/jats:italic>\n            conditions, the\n            <jats:italic>rhr2<\/jats:italic>\n            \u0394\/\u0394 mutant has reduced biofilm biomass and reduced adherence to silicone. The\n            <jats:italic>rhr2<\/jats:italic>\n            \u0394\/\u0394 mutant is also severely defective in biofilm formation\n            <jats:italic>in vivo<\/jats:italic>\n            in a rat catheter infection model. Expression profiling indicates that the\n            <jats:italic>rhr2<\/jats:italic>\n            \u0394\/\u0394 mutant has reduced expression of cell surface adhesin genes\n            <jats:italic>ALS1<\/jats:italic>\n            ,\n            <jats:italic>ALS3<\/jats:italic>\n            , and\n            <jats:italic>HWP1<\/jats:italic>\n            , as well as many other biofilm-upregulated genes. Reduced adhesin expression may be the cause of the\n            <jats:italic>rhr2<\/jats:italic>\n            \u0394\/\u0394 mutant biofilm defect, because overexpression of\n            <jats:italic>ALS1<\/jats:italic>\n            ,\n            <jats:italic>ALS3<\/jats:italic>\n            , or\n            <jats:italic>HWP1<\/jats:italic>\n            restores biofilm formation ability to the mutant\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            . Our findings indicate that internal glycerol has a regulatory role in biofilm gene expression and that adhesin genes are among the main functional Rhr2-regulated genes.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:named-content content-type=\"genus-species\">Candida albicans<\/jats:named-content>\n            is a major fungal pathogen, and infection can arise from the therapeutically intractable biofilms that it forms on medically implanted devices. It stands to reason that genes whose expression is induced during biofilm growth will function in the process, and our analysis of 25 such genes confirms that expectation. One gene is involved in synthesis of glycerol, a small metabolite that we find is abundant in biofilm cells. The impact of glycerol on biofilm formation is regulatory, not solely metabolic, because it is required for expression of numerous biofilm-associated genes. Restoration of expression of three of these genes that specify cell surface adhesins enables the glycerol-synthetic mutant to create a biofilm. Our findings emphasize the significance of metabolic pathways as therapeutic targets, because their disruption can have both physiological and regulatory consequences.\n          <\/jats:p>","DOI":"10.1128\/mbio.00637-12","type":"journal-article","created":{"date-parts":[[2013,4,10]],"date-time":"2013-04-10T03:28:56Z","timestamp":1365564536000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":80,"title":["Regulatory Role of Glycerol in Candida albicans Biofilm Formation"],"prefix":"10.1128","volume":"4","author":[{"given":"Jigar V.","family":"Desai","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent M.","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland, School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shantanu","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Stamper","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin F.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"Solis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott G.","family":"Filler","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Andes","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saranna","family":"Fanning","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Lanni","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron P.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/441300a"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.59.110106.132000"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2475"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.59.030804.121034"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir077"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.2.255-267.2004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00103-12"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2011.06.001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05126-11"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","unstructured":"M\u00e9anM\nMarchettiO\nCalandraT\n. 2008. Bench-to-bedside review: Candida infections in the intensive care unit. Crit. Care 12:204. http:\/\/dx.doi.org\/10.1186\/cc6425.","DOI":"10.1186\/cc6212"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05196-11"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02765-05"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","unstructured":"UppuluriP\nChaturvediAK\nSrinivasanA\nBanerjeeM\nRamasubramaniamAK\nK\u00f6hlerJR\nKadoshD\nLopez-RibotJL\n. 2010. Dispersion as an important step in the Candida albicans biofilm developmental cycle. PLoS Pathog. 6:e1000828. http:\/\/dx.doi.org\/10.1371\/journal.ppat.1000828.","DOI":"10.1371\/journal.ppat.1000828"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00111-10"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.64.4.847-867.2000"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07626.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.048"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.05.047"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","unstructured":"NobileCJ\nNettJE\nHerndayAD\nHomannOR\nDeneaultJS\nNantelA\nAndesDR\nJohnsonAD\nMitchellAP\n. 2009. Biofilm matrix regulation by Candida albicans Zap1. PLoS Biol. 7:e1000133. http:\/\/dx.doi.org\/10.1371\/journal.pbio.1000133.","DOI":"10.1371\/journal.pbio.1000133"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00314-07"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.8.1493-1502.2005"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","unstructured":"TaffHT\nNettJE\nZarnowskiR\nRossKM\nSanchezH\nCainMT\nHamakerJ\nMitchellAP\nAndesDR\n. 2012. A Candida biofilm-induced pathway for matrix glucan delivery: implications for drug resistance. PLoS Pathog. 8:e1002848. http:\/\/dx.doi.org\/10.1371\/journal.ppat.1002848.","DOI":"10.1371\/journal.ppat.1002848"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.2.536-545.2004"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08064"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401648101"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.169.1.189-197.1987"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsle.2005.02.031"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01955.x"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.10.6023-6031.2004"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.11.3195-3197.2001"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","unstructured":"NobileCJ\nAndesDR\nNettJE\nSmithFJ\nYueF\nPhanQT\nEdwardsJE\nFillerSG\nMitchellAP\n. 2006. Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation in vitro and in vivo . PLoS Pathog. 2:e63. http:\/\/dx.doi.org\/10.1371\/journal.ppat.0020063.","DOI":"10.1371\/journal.ppat.0020063"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.9.1562-1573.2005"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/006163-0"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.11.5601-5613.2005"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.59.030804.121310"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.3.390-397.2003"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00194-06"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.06.034"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.28959-0"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R700042200"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02757.x"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.23.7243-7247.1999"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi900886g"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00323-08"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2008.00404.x"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05438.x"},{"key":"e_1_3_2_48_2","doi-asserted-by":"crossref","unstructured":"FinkelJS\nXuW\nHuangD\nHillEM\nDesaiJV\nWoolfordCA\nNettJE\nTaffH\nNoriceCT\nAndesDR\nLanniF\nMitchellAP\n. 2012. Portrait of Candida albicans adherence regulators. PLoS Pathog. 8:e1002525. http:\/\/dx.doi.org\/10.1371\/journal.ppat.1002525.","DOI":"10.1371\/journal.ppat.1002525"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.112.144485"},{"key":"e_1_3_2_50_2","doi-asserted-by":"crossref","unstructured":"BlankenshipJR\nFanningS\nHamakerJJ\nMitchellAP\n. 2010. An extensive circuitry for cell wall regulation in Candida albicans. PLoS Pathog. 6:e1000752. http:\/\/dx.doi.org\/10.1371\/journal.ppat.1000752.","DOI":"10.1371\/journal.ppat.1000752"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.109553.110"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07517"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp120"},{"key":"e_1_3_2_54_2","doi-asserted-by":"crossref","unstructured":"AndersS\nHuberW\n. 2010. Differential expression analysis for sequence count data. Genome Biol. 11:R106. http:\/\/dx.doi.org\/10.1186\/gb-2010-11-10-r106.","DOI":"10.1186\/gb-2010-11-10-r106"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00637-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00637-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T01:51:37Z","timestamp":1646704297000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.00637-12"}},"subtitle":[],"editor":[{"given":"Jose","family":"Lopez-Ribot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Judith","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,5]]},"references-count":53,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1128\/mBio.00637-12"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00637-12","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5]]},"assertion":[{"value":"2013-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-03-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-04-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00637-12"}}