Ifu5, a WW domain‐containing protein interacts with Efg1 to achieve coordination of normoxic and hypoxic functions to influence pathogenicity traits in Candida albicans
Hypoxic adaptation pathways, essential for Candida albicans pathogenesis, are tied to its transition from a commensal to a pathogen. Herein, we identify a WW domain‐containing protein, Ifu5, as a determinant of hypoxic adaptation that also impacts normoxic responses in this fungus. Ifu5 activity sup...
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| Veröffentlicht in: | Cellular microbiology 2020-02, Vol.22 (2), p.e13140-n/a |
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| creator | Rastogi, Sumit K. Wijlick, Lasse Ror, Shivani Lee, Keunsook K. Román, Elvira Agarwal, Pranjali Manzoor, Nikhat Gow, Neil A.R. Pla, Jesús Ernst, Joachim F. Panwar, Sneh L. |
| description | Hypoxic adaptation pathways, essential for Candida albicans pathogenesis, are tied to its transition from a commensal to a pathogen. Herein, we identify a WW domain‐containing protein, Ifu5, as a determinant of hypoxic adaptation that also impacts normoxic responses in this fungus. Ifu5 activity supports glycosylation homeostasis via the Cek1 mitogen‐activated protein kinase‐dependent up‐regulation of PMT1, under normoxia. Transcriptome analysis of ifu5Δ/Δ under normoxia shows a significant up‐regulation of the hypoxic regulator EFG1 and EFG1‐dependent genes. We demonstrate physical interaction between Ifu5 by virtue of its WW domain and Efg1 that represses EFG1 expression under normoxia. This interaction is lost under hypoxic growth conditions, relieving EFG1 repression. Hypoxic adaptation processes such as filamentation and biofilm formation are affected in ifu5Δ/Δ cells revealing the role of Ifu5 in hypoxic signalling and modulating pathogenicity traits of C. albicans under varied oxygen conditions. Additionally, the WW domain of Ifu5 facilitates its role in hypoxic adaptation, revealing the importance of this domain in providing a platform to integrate various cellular processes. These data forge a relationship between Efg1 and Ifu5 that fosters the role of Ifu5 in hypoxic adaptation thus illuminating novel strategies to undermine the growth of C. albicans. |
| doi_str_mv | 10.1111/cmi.13140 |
| format | Article |
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Herein, we identify a WW domain‐containing protein, Ifu5, as a determinant of hypoxic adaptation that also impacts normoxic responses in this fungus. Ifu5 activity supports glycosylation homeostasis via the Cek1 mitogen‐activated protein kinase‐dependent up‐regulation of PMT1, under normoxia. Transcriptome analysis of ifu5Δ/Δ under normoxia shows a significant up‐regulation of the hypoxic regulator EFG1 and EFG1‐dependent genes. We demonstrate physical interaction between Ifu5 by virtue of its WW domain and Efg1 that represses EFG1 expression under normoxia. This interaction is lost under hypoxic growth conditions, relieving EFG1 repression. Hypoxic adaptation processes such as filamentation and biofilm formation are affected in ifu5Δ/Δ cells revealing the role of Ifu5 in hypoxic signalling and modulating pathogenicity traits of C. albicans under varied oxygen conditions. Additionally, the WW domain of Ifu5 facilitates its role in hypoxic adaptation, revealing the importance of this domain in providing a platform to integrate various cellular processes. These data forge a relationship between Efg1 and Ifu5 that fosters the role of Ifu5 in hypoxic adaptation thus illuminating novel strategies to undermine the growth of C. albicans.</description><identifier>ISSN: 1462-5814</identifier><identifier>EISSN: 1462-5822</identifier><identifier>DOI: 10.1111/cmi.13140</identifier><identifier>PMID: 31736226</identifier><language>eng</language><publisher>India: Hindawi Limited</publisher><subject>Adaptation ; Biofilm ; Biofilms ; Candida albicans ; Candida albicans - pathogenicity ; cell wall integrity ; DNA-Binding Proteins - metabolism ; Efg1 ; Filamentation ; Fungal Proteins - metabolism ; Fungi ; Gene expression ; Gene Expression Regulation, Fungal ; Glycosylation ; Growth conditions ; Homeostasis ; Hyphae ; hyphal morphogenesis ; Hypoxia ; Kinases ; Pathogenesis ; Pathogenicity ; Pathogens ; Protein kinase ; Proteins ; Signal transduction ; Transcription Factors - metabolism ; Virulence ; Virulence Factors - metabolism ; WW domain ; WW Domains</subject><ispartof>Cellular microbiology, 2020-02, Vol.22 (2), p.e13140-n/a</ispartof><rights>2019 John Wiley & Sons Ltd</rights><rights>2019 John Wiley & Sons Ltd.</rights><rights>2020 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3530-569c6ca27cd102302a4ce512e34d221394f44357c31bcd705bef702c0b6ff7593</citedby><cites>FETCH-LOGICAL-c3530-569c6ca27cd102302a4ce512e34d221394f44357c31bcd705bef702c0b6ff7593</cites><orcidid>0000-0003-0848-8306</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcmi.13140$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcmi.13140$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31736226$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rastogi, Sumit K.</creatorcontrib><creatorcontrib>Wijlick, Lasse</creatorcontrib><creatorcontrib>Ror, Shivani</creatorcontrib><creatorcontrib>Lee, Keunsook K.</creatorcontrib><creatorcontrib>Román, Elvira</creatorcontrib><creatorcontrib>Agarwal, Pranjali</creatorcontrib><creatorcontrib>Manzoor, Nikhat</creatorcontrib><creatorcontrib>Gow, Neil A.R.</creatorcontrib><creatorcontrib>Pla, Jesús</creatorcontrib><creatorcontrib>Ernst, Joachim F.</creatorcontrib><creatorcontrib>Panwar, Sneh L.</creatorcontrib><title>Ifu5, a WW domain‐containing protein interacts with Efg1 to achieve coordination of normoxic and hypoxic functions to influence pathogenicity traits in Candida albicans</title><title>Cellular microbiology</title><addtitle>Cell Microbiol</addtitle><description>Hypoxic adaptation pathways, essential for Candida albicans pathogenesis, are tied to its transition from a commensal to a pathogen. Herein, we identify a WW domain‐containing protein, Ifu5, as a determinant of hypoxic adaptation that also impacts normoxic responses in this fungus. Ifu5 activity supports glycosylation homeostasis via the Cek1 mitogen‐activated protein kinase‐dependent up‐regulation of PMT1, under normoxia. Transcriptome analysis of ifu5Δ/Δ under normoxia shows a significant up‐regulation of the hypoxic regulator EFG1 and EFG1‐dependent genes. We demonstrate physical interaction between Ifu5 by virtue of its WW domain and Efg1 that represses EFG1 expression under normoxia. This interaction is lost under hypoxic growth conditions, relieving EFG1 repression. Hypoxic adaptation processes such as filamentation and biofilm formation are affected in ifu5Δ/Δ cells revealing the role of Ifu5 in hypoxic signalling and modulating pathogenicity traits of C. albicans under varied oxygen conditions. Additionally, the WW domain of Ifu5 facilitates its role in hypoxic adaptation, revealing the importance of this domain in providing a platform to integrate various cellular processes. These data forge a relationship between Efg1 and Ifu5 that fosters the role of Ifu5 in hypoxic adaptation thus illuminating novel strategies to undermine the growth of C. albicans.</description><subject>Adaptation</subject><subject>Biofilm</subject><subject>Biofilms</subject><subject>Candida albicans</subject><subject>Candida albicans - pathogenicity</subject><subject>cell wall integrity</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Efg1</subject><subject>Filamentation</subject><subject>Fungal Proteins - metabolism</subject><subject>Fungi</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Fungal</subject><subject>Glycosylation</subject><subject>Growth conditions</subject><subject>Homeostasis</subject><subject>Hyphae</subject><subject>hyphal morphogenesis</subject><subject>Hypoxia</subject><subject>Kinases</subject><subject>Pathogenesis</subject><subject>Pathogenicity</subject><subject>Pathogens</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Transcription Factors - metabolism</subject><subject>Virulence</subject><subject>Virulence Factors - metabolism</subject><subject>WW domain</subject><subject>WW Domains</subject><issn>1462-5814</issn><issn>1462-5822</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1uFDEQha0IRH5gkQtEltiAxCT-abtnlmgUwkhBbEBZttzV9kxF3fZguwmzyxFyjhwrJ8GTSbJAojb1Fl-9qtIj5JizU17qDAY85ZJXbI8c8EqLiZoK8epF82qfHKZ0zRjXNedvyL7ktdRC6ANyv3Cj-kQNvbqiXRgM-ofbOwg-F4V-SdcxZIueos82GsiJ3mBe0XO35DQHamCF9relEELs0JuMwdPgqA9xCH8QqPEdXW3Wj9qNHrZA2k6id_1oPVi6NnkVltYjYN7QHA2WLWXlvMxiZ6jpWwTj01vy2pk-2XdP_Yj8_HL-Y_51cvn9YjH_fDkBqSSbKD0DDUbU0HEmJBOmAqu4sLLqhOByVrmqkqoGyVvoaqZa62omgLXauVrN5BH5sPMtv_8abcrNgAls3xtvw5gaIblSQrOpLuj7f9DrMEZfriuUnNZsyiQr1McdBTGkFK1r1hEHEzcNZ802wKYE2DwGWNiTJ8exHWz3Qj4nVoCzHXCDvd3836mZf1vsLP8CHqOnRw</recordid><startdate>202002</startdate><enddate>202002</enddate><creator>Rastogi, Sumit K.</creator><creator>Wijlick, Lasse</creator><creator>Ror, Shivani</creator><creator>Lee, Keunsook K.</creator><creator>Román, Elvira</creator><creator>Agarwal, Pranjali</creator><creator>Manzoor, Nikhat</creator><creator>Gow, Neil A.R.</creator><creator>Pla, Jesús</creator><creator>Ernst, Joachim F.</creator><creator>Panwar, Sneh L.</creator><general>Hindawi Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0848-8306</orcidid></search><sort><creationdate>202002</creationdate><title>Ifu5, a WW domain‐containing protein interacts with Efg1 to achieve coordination of normoxic and hypoxic functions to influence pathogenicity traits in Candida albicans</title><author>Rastogi, Sumit K. ; 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Herein, we identify a WW domain‐containing protein, Ifu5, as a determinant of hypoxic adaptation that also impacts normoxic responses in this fungus. Ifu5 activity supports glycosylation homeostasis via the Cek1 mitogen‐activated protein kinase‐dependent up‐regulation of PMT1, under normoxia. Transcriptome analysis of ifu5Δ/Δ under normoxia shows a significant up‐regulation of the hypoxic regulator EFG1 and EFG1‐dependent genes. We demonstrate physical interaction between Ifu5 by virtue of its WW domain and Efg1 that represses EFG1 expression under normoxia. This interaction is lost under hypoxic growth conditions, relieving EFG1 repression. Hypoxic adaptation processes such as filamentation and biofilm formation are affected in ifu5Δ/Δ cells revealing the role of Ifu5 in hypoxic signalling and modulating pathogenicity traits of C. albicans under varied oxygen conditions. Additionally, the WW domain of Ifu5 facilitates its role in hypoxic adaptation, revealing the importance of this domain in providing a platform to integrate various cellular processes. These data forge a relationship between Efg1 and Ifu5 that fosters the role of Ifu5 in hypoxic adaptation thus illuminating novel strategies to undermine the growth of C. albicans.</abstract><cop>India</cop><pub>Hindawi Limited</pub><pmid>31736226</pmid><doi>10.1111/cmi.13140</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-0848-8306</orcidid></addata></record> |
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| subjects | Adaptation Biofilm Biofilms Candida albicans Candida albicans - pathogenicity cell wall integrity DNA-Binding Proteins - metabolism Efg1 Filamentation Fungal Proteins - metabolism Fungi Gene expression Gene Expression Regulation, Fungal Glycosylation Growth conditions Homeostasis Hyphae hyphal morphogenesis Hypoxia Kinases Pathogenesis Pathogenicity Pathogens Protein kinase Proteins Signal transduction Transcription Factors - metabolism Virulence Virulence Factors - metabolism WW domain WW Domains |
| title | Ifu5, a WW domain‐containing protein interacts with Efg1 to achieve coordination of normoxic and hypoxic functions to influence pathogenicity traits in Candida albicans |
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