{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T10:59:33Z","timestamp":1781607573998,"version":"3.54.5"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"MOH | National Medical Research Council","award":["OFIRG\/0072\/2018"],"award-info":[{"award-number":["OFIRG\/0072\/2018"]}]},{"name":"MOH | National Medical Research Council","award":["OFIRG21jun-0058"],"award-info":[{"award-number":["OFIRG21jun-0058"]}]},{"name":"MOH | National Medical Research Council","award":["OFIRG23Jul-0077"],"award-info":[{"award-number":["OFIRG23Jul-0077"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,2,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Candida albicans<\/jats:italic>\n              , the most frequently isolated fungal pathogen in humans, forms biofilms that enhance resistance to antifungal drugs and host immunity, leading to frequent treatment failure. Understanding the molecular mechanisms governing biofilm formation is crucial for developing anti-biofilm therapies. In this study, we conducted a genetic screen to identify novel genes that regulate biofilm formation in\n              <jats:italic>C. albicans<\/jats:italic>\n              . One identified gene is\n              <jats:italic>ORF19.6693<\/jats:italic>\n              , a homolog of the\n              <jats:italic>Saccharomyces cerevisiae SDD3<\/jats:italic>\n              gene. The\n              <jats:italic>sdd3<\/jats:italic>\n              \u2206\/\u2206 mutant exhibited severe defects in biofilm formation and significantly reduced chitin content in the cell wall. Overexpression of the constitutively active version of the Rho1 GTPase Rho1\n              <jats:sup>G18V<\/jats:sup>\n              , an upstream activator of the protein kinase C (PKC)-mitogen-activated protein kinase (MAPK) cell-wall integrity pathway, rescued these defects. Affinity purification, mass spectrometry, and co-immunoprecipitation revealed Sdd3\u2019s physical interaction with Bem2, the GTPase-activating protein of Rho1. Deletion of\n              <jats:italic>SDD3<\/jats:italic>\n              significantly reduced the amount of the active GTP-bound form of Rho1, thereby diminishing PKC-MAPK signaling and downregulating chitin synthase genes\n              <jats:italic>CHS2<\/jats:italic>\n              and\n              <jats:italic>CHS8<\/jats:italic>\n              . Taken together, our studies identify a new biofilm regulator, Sdd3, in\n              <jats:italic>C. albicans<\/jats:italic>\n              that modulates Rho1 activity through its inhibitory interaction with Bem2, thereby regulating the PKC-MAPK pathway to control chitin biosynthesis, which is critical for biofilm formation. As an upstream component of the pathway and lacking a homolog in mammals, Sdd3 has the potential to serve as an antifungal target for biofilm infections.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                The human fungal pathogen\n                <jats:italic>Candida albicans<\/jats:italic>\n                is categorized as a critical priority pathogen on the World Health Organization\u2019s Fungal Priority Pathogens List. A key virulence attribute of this pathogen is its ability to form biofilms on the surfaces of indwelling medical devices. Fungal cells in biofilms are highly resistant to antifungal drugs and host immunity, leading to treatment failure. This study conducted a genetic screen to discover novel genes that regulate biofilm formation. We found that deletion of the\n                <jats:italic>SDD3<\/jats:italic>\n                gene caused severe biofilm defects. Sdd3 negatively regulates the Rho1 GTPase, an upstream activator of the protein kinase C-mitogen-activated protein kinase pathway, through direct interaction with Bem2, the GTPase-activating protein of Rho1, resulting in a significant decrease in chitin content in the fungal cell wall. This chitin synthesis defect leads to biofilm formation failure. Given its essential role in biofilm formation, Sdd3 could serve as an antifungal target for biofilm infections.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/mbio.03283-24","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T14:00:35Z","timestamp":1734444035000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Sdd3 regulates the biofilm formation of\n            <i>Candida albicans<\/i>\n            via the Rho1-PKC-MAPK pathway"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9001-9068","authenticated-orcid":false,"given":"Li Mei","family":"Pang","sequence":"first","affiliation":[{"name":"A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR)","place":["Singapore, Singapore"]},{"name":"Singapore Oral Microbiomics Initiative, National Dental Research Institute Singapore, National Dental Center Singapore","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8920-5525","authenticated-orcid":true,"given":"Guisheng","family":"Zeng","sequence":"additional","affiliation":[{"name":"A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR)","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve Wai Ling","family":"Chow","sequence":"additional","affiliation":[{"name":"A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR)","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Xu","sequence":"additional","affiliation":[{"name":"A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR)","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR)","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Jiun","family":"Kok","sequence":"additional","affiliation":[{"name":"Bioprocessing Technology Institute","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu Chen","family":"Chong","sequence":"additional","affiliation":[{"name":"A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR)","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhi","family":"Bi","sequence":"additional","affiliation":[{"name":"Bioprocessing Technology Institute","place":["Singapore, Singapore"]},{"name":"Duke-NUS Medical School, National University of Singapore","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology, Institute of Microbiology","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0816-538X","authenticated-orcid":false,"given":"Chaminda Jayampath","family":"Seneviratne","sequence":"additional","affiliation":[{"name":"Singapore Oral Microbiomics Initiative, National Dental Research Institute Singapore, National Dental Center Singapore","place":["Singapore, Singapore"]},{"name":"Oral Health ACP, Duke NUS Medical School","place":["Singapore, Singapore"]},{"name":"School of Dentistry, The University of Queensland","place":["St Lucia, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1211-2822","authenticated-orcid":true,"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR)","place":["Singapore, Singapore"]},{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00076-09"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms5020032"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00034-10"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/10454411940050020101"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuaa060"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0011-8532(22)02484-3"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.26"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004404"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2014.09.001"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.4161\/viru.22913"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2019.04.001"},{"key":"e_1_3_6_13_2","volume-title":"Microbial biofilms: omics biology, antimicrobials and clinical implications","author":"Seneviratne CJ","year":"2017","unstructured":"Seneviratne CJ, Truong T, Wang Y. 2017. Candida biofilms: properties, antifungal resistance and novel therapeutic options. In Seneviratne CJ (ed), Microbial biofilms: omics biology, antimicrobials and clinical implications. CRC Press."},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.107"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00068-15"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-091014-104330"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-023-00796-x"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.048"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006948"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13002"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00094-13"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2002.tb11330.x"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2012.08193.x"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.4.2197"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-144-2-411"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407097102"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.FUNK-0035-2016"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.47.100193.002445"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-407678-5.00004-0"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05588.x"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2021.103813"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01766-19"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03082-4"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082395"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004542"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.638609"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06944-1"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0351-3"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020063"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00028"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2002.tb00613.x"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.4.5.807"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19246-9"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.21.020604.150721"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1080\/mmy.39.1.111.121"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10070859"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcsw.2021.100057"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2010.05.002"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-146-9-2121"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.127.5.1395"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11865"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06944-1"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.029"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-017-0043-0"},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.1534\/g3.117.300388"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep12433"},{"key":"e_1_3_6_57_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M116.061523"},{"key":"e_1_3_6_58_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00164"},{"key":"e_1_3_6_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201900240"},{"key":"e_1_3_6_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113473"},{"key":"e_1_3_6_61_2","doi-asserted-by":"publisher","DOI":"10.1534\/g3.114.010892"},{"key":"e_1_3_6_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00796-9"},{"key":"e_1_3_6_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.4.633-638.2005"},{"key":"e_1_3_6_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpmc.60"},{"key":"e_1_3_6_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142727.mb1312s23"},{"key":"e_1_3_6_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.468"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03283-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03283-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T14:07:47Z","timestamp":1738764467000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.03283-24"}},"subtitle":[],"editor":[{"given":"Judith","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":65,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2,5]]}},"alternative-id":["10.1128\/mbio.03283-24"],"URL":"https:\/\/doi.org\/10.1128\/mbio.03283-24","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]},"assertion":[{"value":"2024-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03283-24"}}