Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei
Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or i...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2016-08, Vol.10 (8), p.e0004907-e0004907 |
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| creator | Woo, Patrick C Y Lau, Susanna K P Lau, Candy C Y Tung, Edward T K Chong, Ken T K Yang, Fengjuan Zhang, Hongmin Lo, Raymond K C Cai, Jian-Pao Au-Yeung, Rex K H Ng, Wing-Fung Tse, Herman Wong, Samson S Y Xu, Simin Lam, Wai Hei Tse, Man-Kit Sze, Kong Hung Kao, Richard Y Reiner, Neil E Hao, Quan Yuen, Kwok-Yung |
| description | Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors.
We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days after challenge with wild-type T. marneffei PM1 and MP1 complemented mutant respectively. None of the mice died 60 days after challenge with MP1 knockout mutant (P |
| doi_str_mv | 10.1371/journal.pntd.0004907 |
| format | Article |
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We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days after challenge with wild-type T. marneffei PM1 and MP1 complemented mutant respectively. None of the mice died 60 days after challenge with MP1 knockout mutant (P<0.0001). Seventy percent of mice died 60 days after challenge with MP1 knockdown mutant (P<0.0001). All mice died after challenge with MPLP1 to MPLP13 knockdown mutants, suggesting that only Mp1p plays a significant role in virulence. The mean fungal loads of PM1 and MP1 complemented mutant in the liver, lung, kidney and spleen were significantly higher than those of the MP1 knockout mutant. Similarly, the mean load of PM1 in the liver, lung and spleen were significantly higher than that of the MP1 knockdown mutant. Histopathological studies showed an abundance of yeast in the kidney, spleen, liver and lung with more marked hepatic and splenic necrosis in mice challenged with PM1 compared to MP1 knockout and MP1 knockdown mutants. Likewise, a higher abundance of yeast was observed in the liver and spleen of mice challenged with MP1 complemented mutant compared to MP1 knockout mutant. PM1 and MP1 complemented mutant survived significantly better than MP1 knockout mutant in macrophages at 48 hours (P<0.01) post-infection. The mean fungal counts of Pichia pastoris GS115-MP1 in the liver (P<0.001) and spleen (P<0.05) of mice were significantly higher than those of GS115 at 24 hours post-challenge.
Mp1p is a key virulence factor of T. marneffei. Mp1p mediates virulence by improving the survival of T. marneffei in macrophages.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0004907</identifier><identifier>PMID: 27560160</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Antigens, Fungal - genetics ; Antigens, Fungal - immunology ; Biology and Life Sciences ; Colleges & universities ; Experiments ; Fatalities ; Fungi ; Gangrene ; Gene Knockdown Techniques ; Genomes ; HIV ; Human immunodeficiency virus ; Humans ; Infections ; Kidney - microbiology ; Kidneys ; Liver ; Liver - microbiology ; Liver - pathology ; Lung - microbiology ; Macrophages - microbiology ; Medical research ; Medicine and Health Sciences ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - immunology ; Mice ; Mutants ; Mutation ; Mycoses - immunology ; Penicillium ; Penicillium marneffei ; Pichia - growth & development ; Pichia - physiology ; Pichia pastoris ; Prevalence studies (Epidemiology) ; Proteins ; Research and Analysis Methods ; Scholarships & fellowships ; Spleen ; Spleen - microbiology ; Spleen - pathology ; Talaromyces ; Talaromyces - genetics ; Talaromyces - growth & development ; Talaromyces - pathogenicity ; Tropical diseases ; Virulence (Microbiology) ; Virulence Factors - genetics ; Virulence Factors - immunology ; Virulence Factors - isolation & purification ; Yeasts</subject><ispartof>PLoS neglected tropical diseases, 2016-08, Vol.10 (8), p.e0004907-e0004907</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: . PLoS Negl Trop Dis 10(8): e0004907. doi:10.1371/journal.pntd.0004907</rights><rights>2016 Woo et al 2016 Woo et al</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: . PLoS Negl Trop Dis 10(8): e0004907. doi:10.1371/journal.pntd.0004907</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c723t-d59270808fa59d0d65bc297354a4d43cd512934af7810fd2eb8d3e6d17b5436f3</citedby><cites>FETCH-LOGICAL-c723t-d59270808fa59d0d65bc297354a4d43cd512934af7810fd2eb8d3e6d17b5436f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999278/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999278/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27560160$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Vinetz, Joseph M.</contributor><creatorcontrib>Woo, Patrick C Y</creatorcontrib><creatorcontrib>Lau, Susanna K P</creatorcontrib><creatorcontrib>Lau, Candy C Y</creatorcontrib><creatorcontrib>Tung, Edward T K</creatorcontrib><creatorcontrib>Chong, Ken T K</creatorcontrib><creatorcontrib>Yang, Fengjuan</creatorcontrib><creatorcontrib>Zhang, Hongmin</creatorcontrib><creatorcontrib>Lo, Raymond K C</creatorcontrib><creatorcontrib>Cai, Jian-Pao</creatorcontrib><creatorcontrib>Au-Yeung, Rex K H</creatorcontrib><creatorcontrib>Ng, Wing-Fung</creatorcontrib><creatorcontrib>Tse, Herman</creatorcontrib><creatorcontrib>Wong, Samson S Y</creatorcontrib><creatorcontrib>Xu, Simin</creatorcontrib><creatorcontrib>Lam, Wai Hei</creatorcontrib><creatorcontrib>Tse, Man-Kit</creatorcontrib><creatorcontrib>Sze, Kong Hung</creatorcontrib><creatorcontrib>Kao, Richard Y</creatorcontrib><creatorcontrib>Reiner, Neil E</creatorcontrib><creatorcontrib>Hao, Quan</creatorcontrib><creatorcontrib>Yuen, Kwok-Yung</creatorcontrib><title>Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors.
We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days after challenge with wild-type T. marneffei PM1 and MP1 complemented mutant respectively. None of the mice died 60 days after challenge with MP1 knockout mutant (P<0.0001). Seventy percent of mice died 60 days after challenge with MP1 knockdown mutant (P<0.0001). All mice died after challenge with MPLP1 to MPLP13 knockdown mutants, suggesting that only Mp1p plays a significant role in virulence. The mean fungal loads of PM1 and MP1 complemented mutant in the liver, lung, kidney and spleen were significantly higher than those of the MP1 knockout mutant. Similarly, the mean load of PM1 in the liver, lung and spleen were significantly higher than that of the MP1 knockdown mutant. Histopathological studies showed an abundance of yeast in the kidney, spleen, liver and lung with more marked hepatic and splenic necrosis in mice challenged with PM1 compared to MP1 knockout and MP1 knockdown mutants. Likewise, a higher abundance of yeast was observed in the liver and spleen of mice challenged with MP1 complemented mutant compared to MP1 knockout mutant. PM1 and MP1 complemented mutant survived significantly better than MP1 knockout mutant in macrophages at 48 hours (P<0.01) post-infection. The mean fungal counts of Pichia pastoris GS115-MP1 in the liver (P<0.001) and spleen (P<0.05) of mice were significantly higher than those of GS115 at 24 hours post-challenge.
Mp1p is a key virulence factor of T. marneffei. Mp1p mediates virulence by improving the survival of T. marneffei in macrophages.</description><subject>Analysis</subject><subject>Animals</subject><subject>Antigens, Fungal - genetics</subject><subject>Antigens, Fungal - immunology</subject><subject>Biology and Life Sciences</subject><subject>Colleges & universities</subject><subject>Experiments</subject><subject>Fatalities</subject><subject>Fungi</subject><subject>Gangrene</subject><subject>Gene Knockdown Techniques</subject><subject>Genomes</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infections</subject><subject>Kidney - microbiology</subject><subject>Kidneys</subject><subject>Liver</subject><subject>Liver - microbiology</subject><subject>Liver - pathology</subject><subject>Lung - microbiology</subject><subject>Macrophages - microbiology</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - immunology</subject><subject>Mice</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Mycoses - immunology</subject><subject>Penicillium</subject><subject>Penicillium marneffei</subject><subject>Pichia - growth & development</subject><subject>Pichia - physiology</subject><subject>Pichia pastoris</subject><subject>Prevalence studies (Epidemiology)</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Scholarships & fellowships</subject><subject>Spleen</subject><subject>Spleen - microbiology</subject><subject>Spleen - pathology</subject><subject>Talaromyces</subject><subject>Talaromyces - genetics</subject><subject>Talaromyces - growth & development</subject><subject>Talaromyces - pathogenicity</subject><subject>Tropical diseases</subject><subject>Virulence (Microbiology)</subject><subject>Virulence Factors - genetics</subject><subject>Virulence Factors - immunology</subject><subject>Virulence Factors - isolation & purification</subject><subject>Yeasts</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNUk1vEzEQtRCIlsA_QLASEiqHBH-u1xekqKIQqQgOhavl9UfiyLsO9i5S_z1Os60S1AP2wdb4vTdvxgPAawQXiHD0cRvH1Kuw2PWDWUAIqYD8CThHgrA55oQ9PbqfgRc5byFkgjXoOTjDnNUQ1fAcLL_t0K5a5UpVv3wag-21ra6UHmKqfF_dqKBS7G61zdXFD9t77UPwY_eh6lTqrXPWvwTPnArZvprOGfh59fnm8uv8-vuX1eXyeq45JsPcMIE5bGDjFBMGmpq1GovijSpqKNGGISwIVY43CDqDbdsYYmuDeMsoqR2ZgbcH3V2IWU7VZ4kaDHHDSFkzsDogTFRbuUu-eLyVUXl5F4hpLVUavA5W4rYpqaimrsW0NEJpyhV3FFtotCGoaH2aso1tZ422_ZBUOBE9fen9Rq7jH0mFKIU2ReBiEkjx92jzIDuftQ1B9TaOd755IzBB7D-giNYNgeUnZ-DdP9DHGzGh1qrU6nsXi0W9F5VLygVFokZ1QS0eQZVtbOd1LL_rS_yE8P6IsLEqDJscwzj42OdTID0AdYo5J-se-oag3A_vvWu5H145DW-hvTnu-QPpflrJX2ml6Jc</recordid><startdate>20160825</startdate><enddate>20160825</enddate><creator>Woo, Patrick C Y</creator><creator>Lau, Susanna K P</creator><creator>Lau, Candy C Y</creator><creator>Tung, Edward T K</creator><creator>Chong, Ken T K</creator><creator>Yang, Fengjuan</creator><creator>Zhang, Hongmin</creator><creator>Lo, Raymond K C</creator><creator>Cai, Jian-Pao</creator><creator>Au-Yeung, Rex K H</creator><creator>Ng, Wing-Fung</creator><creator>Tse, Herman</creator><creator>Wong, Samson S Y</creator><creator>Xu, Simin</creator><creator>Lam, Wai Hei</creator><creator>Tse, Man-Kit</creator><creator>Sze, Kong Hung</creator><creator>Kao, Richard Y</creator><creator>Reiner, Neil E</creator><creator>Hao, Quan</creator><creator>Yuen, Kwok-Yung</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>7U2</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160825</creationdate><title>Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei</title><author>Woo, Patrick C Y ; Lau, Susanna K P ; Lau, Candy C Y ; Tung, Edward T K ; Chong, Ken T K ; Yang, Fengjuan ; Zhang, Hongmin ; Lo, Raymond K C ; Cai, Jian-Pao ; Au-Yeung, Rex K H ; Ng, Wing-Fung ; Tse, Herman ; Wong, Samson S Y ; Xu, Simin ; Lam, Wai Hei ; Tse, Man-Kit ; Sze, Kong Hung ; Kao, Richard Y ; Reiner, Neil E ; Hao, Quan ; Yuen, Kwok-Yung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c723t-d59270808fa59d0d65bc297354a4d43cd512934af7810fd2eb8d3e6d17b5436f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Antigens, Fungal - 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Academic</collection><collection>Safety Science and Risk</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Woo, Patrick C Y</au><au>Lau, Susanna K P</au><au>Lau, Candy C Y</au><au>Tung, Edward T K</au><au>Chong, Ken T K</au><au>Yang, Fengjuan</au><au>Zhang, Hongmin</au><au>Lo, Raymond K C</au><au>Cai, Jian-Pao</au><au>Au-Yeung, Rex K H</au><au>Ng, Wing-Fung</au><au>Tse, Herman</au><au>Wong, Samson S Y</au><au>Xu, Simin</au><au>Lam, Wai Hei</au><au>Tse, Man-Kit</au><au>Sze, Kong Hung</au><au>Kao, Richard Y</au><au>Reiner, Neil E</au><au>Hao, Quan</au><au>Yuen, Kwok-Yung</au><au>Vinetz, Joseph M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2016-08-25</date><risdate>2016</risdate><volume>10</volume><issue>8</issue><spage>e0004907</spage><epage>e0004907</epage><pages>e0004907-e0004907</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors.
We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days after challenge with wild-type T. marneffei PM1 and MP1 complemented mutant respectively. None of the mice died 60 days after challenge with MP1 knockout mutant (P<0.0001). Seventy percent of mice died 60 days after challenge with MP1 knockdown mutant (P<0.0001). All mice died after challenge with MPLP1 to MPLP13 knockdown mutants, suggesting that only Mp1p plays a significant role in virulence. The mean fungal loads of PM1 and MP1 complemented mutant in the liver, lung, kidney and spleen were significantly higher than those of the MP1 knockout mutant. Similarly, the mean load of PM1 in the liver, lung and spleen were significantly higher than that of the MP1 knockdown mutant. Histopathological studies showed an abundance of yeast in the kidney, spleen, liver and lung with more marked hepatic and splenic necrosis in mice challenged with PM1 compared to MP1 knockout and MP1 knockdown mutants. Likewise, a higher abundance of yeast was observed in the liver and spleen of mice challenged with MP1 complemented mutant compared to MP1 knockout mutant. PM1 and MP1 complemented mutant survived significantly better than MP1 knockout mutant in macrophages at 48 hours (P<0.01) post-infection. The mean fungal counts of Pichia pastoris GS115-MP1 in the liver (P<0.001) and spleen (P<0.05) of mice were significantly higher than those of GS115 at 24 hours post-challenge.
Mp1p is a key virulence factor of T. marneffei. Mp1p mediates virulence by improving the survival of T. marneffei in macrophages.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27560160</pmid><doi>10.1371/journal.pntd.0004907</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2016-08, Vol.10 (8), p.e0004907-e0004907 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_1820285333 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Analysis Animals Antigens, Fungal - genetics Antigens, Fungal - immunology Biology and Life Sciences Colleges & universities Experiments Fatalities Fungi Gangrene Gene Knockdown Techniques Genomes HIV Human immunodeficiency virus Humans Infections Kidney - microbiology Kidneys Liver Liver - microbiology Liver - pathology Lung - microbiology Macrophages - microbiology Medical research Medicine and Health Sciences Membrane Glycoproteins - genetics Membrane Glycoproteins - immunology Mice Mutants Mutation Mycoses - immunology Penicillium Penicillium marneffei Pichia - growth & development Pichia - physiology Pichia pastoris Prevalence studies (Epidemiology) Proteins Research and Analysis Methods Scholarships & fellowships Spleen Spleen - microbiology Spleen - pathology Talaromyces Talaromyces - genetics Talaromyces - growth & development Talaromyces - pathogenicity Tropical diseases Virulence (Microbiology) Virulence Factors - genetics Virulence Factors - immunology Virulence Factors - isolation & purification Yeasts |
| title | Mp1p Is a Virulence Factor in Talaromyces (Penicillium) marneffei |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T13%3A52%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mp1p%20Is%20a%20Virulence%20Factor%20in%20Talaromyces%20(Penicillium)%20marneffei&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Woo,%20Patrick%20C%20Y&rft.date=2016-08-25&rft.volume=10&rft.issue=8&rft.spage=e0004907&rft.epage=e0004907&rft.pages=e0004907-e0004907&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0004907&rft_dat=%3Cgale_plos_%3EA479419616%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1820285333&rft_id=info:pmid/27560160&rft_galeid=A479419616&rft_doaj_id=oai_doaj_org_article_2b84af4c4fb24160ac47a7f42e0dcd31&rfr_iscdi=true |