Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection
Fungal invasion of the oral epithelium is central to the pathogenesis of oropharyngeal candidiasis (OPC). Candida albicans invades the oral epithelium by receptor-induced endocytosis but this process is incompletely understood. We found that C . albicans infection of oral epithelial cells induces c-...
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| Veröffentlicht in: | PLoS pathogens 2023-08, Vol.19 (8), p.e1011579-e1011579 |
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| creator | Phan, Quynh T. Solis, Norma V. Cravener, Max V. Swidergall, Marc Lin, Jianfeng Huang, Manning Y. Liu, Hong Singh, Shakti Ibrahim, Ashraf S. Mazzone, Massimiliano Mitchell, Aaron P. Filler, Scott G. |
| description | Fungal invasion of the oral epithelium is central to the pathogenesis of oropharyngeal candidiasis (OPC).
Candida albicans
invades the oral epithelium by receptor-induced endocytosis but this process is incompletely understood. We found that
C
.
albicans
infection of oral epithelial cells induces c-Met to form a multi-protein complex with E-cadherin and the epidermal growth factor receptor (EGFR). E-cadherin is necessary for
C
.
albicans
to activate both c-Met and EGFR and to induce the endocytosis of
C
.
albicans
. Proteomics analysis revealed that c-Met interacts with
C
.
albicans
Hyr1, Als3 and Ssa1. Both Hyr1 and Als3 are required for
C
.
albicans
to stimulate c-Met and EGFR in oral epithelial cells in vitro and for full virulence during OPC in mice. Treating mice with small molecule inhibitors of c-Met and EGFR ameliorates OPC, demonstrating the potential therapeutic efficacy of blocking these host receptors for
C
.
albicans
. |
| doi_str_mv | 10.1371/journal.ppat.1011579 |
| format | Article |
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Candida albicans
invades the oral epithelium by receptor-induced endocytosis but this process is incompletely understood. We found that
C
.
albicans
infection of oral epithelial cells induces c-Met to form a multi-protein complex with E-cadherin and the epidermal growth factor receptor (EGFR). E-cadherin is necessary for
C
.
albicans
to activate both c-Met and EGFR and to induce the endocytosis of
C
.
albicans
. Proteomics analysis revealed that c-Met interacts with
C
.
albicans
Hyr1, Als3 and Ssa1. Both Hyr1 and Als3 are required for
C
.
albicans
to stimulate c-Met and EGFR in oral epithelial cells in vitro and for full virulence during OPC in mice. Treating mice with small molecule inhibitors of c-Met and EGFR ameliorates OPC, demonstrating the potential therapeutic efficacy of blocking these host receptors for
C
.
albicans
.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1011579</identifier><identifier>PMID: 37611070</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Analysis ; Biology and Life Sciences ; Biotechnology industry ; Candida albicans ; Candidiasis ; Cells ; E-cadherin ; Endocytosis ; Epidermal growth factor ; Epidermal growth factor receptors ; Epithelial cells ; Epithelium ; Growth factors ; Health aspects ; Infection ; Infections ; Kinases ; Ligands ; Medicine and Health Sciences ; Organisms ; Pathogenesis ; Phosphorylation ; Proteomics ; Receptors ; Research and Analysis Methods ; Virulence</subject><ispartof>PLoS pathogens, 2023-08, Vol.19 (8), p.e1011579-e1011579</ispartof><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Phan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Phan et al 2023 Phan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-1281e1948a68ca4157ab79945ba4a6070b01a98629eb6b03545b6e3ba06ac87e3</citedby><cites>FETCH-LOGICAL-c532t-1281e1948a68ca4157ab79945ba4a6070b01a98629eb6b03545b6e3ba06ac87e3</cites><orcidid>0000-0001-7278-3700</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10479894/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10479894/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids></links><search><creatorcontrib>Phan, Quynh T.</creatorcontrib><creatorcontrib>Solis, Norma V.</creatorcontrib><creatorcontrib>Cravener, Max V.</creatorcontrib><creatorcontrib>Swidergall, Marc</creatorcontrib><creatorcontrib>Lin, Jianfeng</creatorcontrib><creatorcontrib>Huang, Manning Y.</creatorcontrib><creatorcontrib>Liu, Hong</creatorcontrib><creatorcontrib>Singh, Shakti</creatorcontrib><creatorcontrib>Ibrahim, Ashraf S.</creatorcontrib><creatorcontrib>Mazzone, Massimiliano</creatorcontrib><creatorcontrib>Mitchell, Aaron P.</creatorcontrib><creatorcontrib>Filler, Scott G.</creatorcontrib><title>Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection</title><title>PLoS pathogens</title><description>Fungal invasion of the oral epithelium is central to the pathogenesis of oropharyngeal candidiasis (OPC).
Candida albicans
invades the oral epithelium by receptor-induced endocytosis but this process is incompletely understood. We found that
C
.
albicans
infection of oral epithelial cells induces c-Met to form a multi-protein complex with E-cadherin and the epidermal growth factor receptor (EGFR). E-cadherin is necessary for
C
.
albicans
to activate both c-Met and EGFR and to induce the endocytosis of
C
.
albicans
. Proteomics analysis revealed that c-Met interacts with
C
.
albicans
Hyr1, Als3 and Ssa1. Both Hyr1 and Als3 are required for
C
.
albicans
to stimulate c-Met and EGFR in oral epithelial cells in vitro and for full virulence during OPC in mice. Treating mice with small molecule inhibitors of c-Met and EGFR ameliorates OPC, demonstrating the potential therapeutic efficacy of blocking these host receptors for
C
.
albicans
.</description><subject>Analysis</subject><subject>Biology and Life Sciences</subject><subject>Biotechnology industry</subject><subject>Candida albicans</subject><subject>Candidiasis</subject><subject>Cells</subject><subject>E-cadherin</subject><subject>Endocytosis</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Infection</subject><subject>Infections</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Medicine and Health Sciences</subject><subject>Organisms</subject><subject>Pathogenesis</subject><subject>Phosphorylation</subject><subject>Proteomics</subject><subject>Receptors</subject><subject>Research and Analysis 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albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection</title><author>Phan, Quynh T. ; Solis, Norma V. ; Cravener, Max V. ; Swidergall, Marc ; Lin, Jianfeng ; Huang, Manning Y. ; Liu, Hong ; Singh, Shakti ; Ibrahim, Ashraf S. ; Mazzone, Massimiliano ; Mitchell, Aaron P. ; Filler, Scott G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-1281e1948a68ca4157ab79945ba4a6070b01a98629eb6b03545b6e3ba06ac87e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analysis</topic><topic>Biology and Life Sciences</topic><topic>Biotechnology industry</topic><topic>Candida albicans</topic><topic>Candidiasis</topic><topic>Cells</topic><topic>E-cadherin</topic><topic>Endocytosis</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptors</topic><topic>Epithelial 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Jianfeng</au><au>Huang, Manning Y.</au><au>Liu, Hong</au><au>Singh, Shakti</au><au>Ibrahim, Ashraf S.</au><au>Mazzone, Massimiliano</au><au>Mitchell, Aaron P.</au><au>Filler, Scott G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection</atitle><jtitle>PLoS pathogens</jtitle><date>2023-08-01</date><risdate>2023</risdate><volume>19</volume><issue>8</issue><spage>e1011579</spage><epage>e1011579</epage><pages>e1011579-e1011579</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Fungal invasion of the oral epithelium is central to the pathogenesis of oropharyngeal candidiasis (OPC).
Candida albicans
invades the oral epithelium by receptor-induced endocytosis but this process is incompletely understood. We found that
C
.
albicans
infection of oral epithelial cells induces c-Met to form a multi-protein complex with E-cadherin and the epidermal growth factor receptor (EGFR). E-cadherin is necessary for
C
.
albicans
to activate both c-Met and EGFR and to induce the endocytosis of
C
.
albicans
. Proteomics analysis revealed that c-Met interacts with
C
.
albicans
Hyr1, Als3 and Ssa1. Both Hyr1 and Als3 are required for
C
.
albicans
to stimulate c-Met and EGFR in oral epithelial cells in vitro and for full virulence during OPC in mice. Treating mice with small molecule inhibitors of c-Met and EGFR ameliorates OPC, demonstrating the potential therapeutic efficacy of blocking these host receptors for
C
.
albicans
.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>37611070</pmid><doi>10.1371/journal.ppat.1011579</doi><orcidid>https://orcid.org/0000-0001-7278-3700</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Public Library of Science (PLoS) Journals Open Access; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Analysis Biology and Life Sciences Biotechnology industry Candida albicans Candidiasis Cells E-cadherin Endocytosis Epidermal growth factor Epidermal growth factor receptors Epithelial cells Epithelium Growth factors Health aspects Infection Infections Kinases Ligands Medicine and Health Sciences Organisms Pathogenesis Phosphorylation Proteomics Receptors Research and Analysis Methods Virulence |
| title | Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection |
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