Glutathione-mediated redox regulation in Cryptococcus neoformans impacts virulence
The fungal pathogen Cryptococcus neoformans is well adapted to its host environment. It has several defence mechanisms to evade oxidative and nitrosative agents released by phagocytic host cells during infection. Among them, melanin production is linked to both fungal virulence and defence against h...
Gespeichert in:
| Veröffentlicht in: | Nature microbiology 2024-08, Vol.9 (8), p.2084-2098 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2098 |
|---|---|
| container_issue | 8 |
| container_start_page | 2084 |
| container_title | Nature microbiology |
| container_volume | 9 |
| creator | Black, Braydon da Silva, Leandro Buffoni Roque Hu, Guanggan Qu, Xianya Smith, Daniel F. Q. Magaña, Armando Alcázar Horianopoulos, Linda C. Caza, Mélissa Attarian, Rodgoun Foster, Leonard J. Casadevall, Arturo Kronstad, James W. |
| description | The fungal pathogen
Cryptococcus neoformans
is well adapted to its host environment. It has several defence mechanisms to evade oxidative and nitrosative agents released by phagocytic host cells during infection. Among them, melanin production is linked to both fungal virulence and defence against harmful free radicals that facilitate host innate immunity. How
C.
neoformans
manipulates its redox environment to facilitate melanin formation and virulence is unclear. Here we show that the antioxidant glutathione is inextricably linked to redox-active processes that facilitate melanin and titan cell production, as well as survival in macrophages and virulence in a murine model of cryptococcosis. Comparative metabolomics revealed that disruption of glutathione biosynthesis leads to accumulation of reducing and acidic compounds in the extracellular environment of mutant cells. Overall, these findings highlight the importance of redox homeostasis and metabolic compensation in pathogen adaptation to the host environment and suggest new avenues for antifungal drug development.
Glutathione metabolism in
Cryptococcus neoformans
influences the redox environment and melanin production, and thus affects fungal virulence. |
| doi_str_mv | 10.1038/s41564-024-01721-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3075376721</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3090081418</sourcerecordid><originalsourceid>FETCH-LOGICAL-c256t-f8b01488c0a9b1377f6d3e0da9a98bdc7c1e4db663b0be31bc918314f8e68d6e3</originalsourceid><addsrcrecordid>eNp9kMtKxDAUhoMozjDOC7iQghs31VzaNF3KoKMwIIiuQ5qcjh3apiatzLy90Y4XXLjIBc53_nP4EDol-JJgJq58QlKexJiGQzJK4u0BmlKcijilGT_89Z-gufcbjDHhlHPBj9GEiTzlNBFT9Lish171L5VtIW7AVKoHEzkwdhvu9VCrPpSiqo0Wbtf1VlutBx-1YEvrGtX6qGo6pXsfvVVuqKHVcIKOSlV7mO_fGXq-vXla3MWrh-X94noVa5ryPi5FgUkihMYqLwjLspIbBtioXOWiMDrTBBJTcM4KXAAjhc6JYCQpBXBhOLAZuhhzO2dfB_C9bCqvoa5V2G7wkuEsZRkPbgJ6_gfd2MG1YbtA5RgLkoTsGaIjpZ313kEpO1c1yu0kwfJDuhylyyBdfkqX29B0to8eiuDvu-VLcQDYCPhQatfgfmb_E_sOhqSORA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3090081418</pqid></control><display><type>article</type><title>Glutathione-mediated redox regulation in Cryptococcus neoformans impacts virulence</title><source>MEDLINE</source><source>Nature</source><source>Alma/SFX Local Collection</source><creator>Black, Braydon ; da Silva, Leandro Buffoni Roque ; Hu, Guanggan ; Qu, Xianya ; Smith, Daniel F. Q. ; Magaña, Armando Alcázar ; Horianopoulos, Linda C. ; Caza, Mélissa ; Attarian, Rodgoun ; Foster, Leonard J. ; Casadevall, Arturo ; Kronstad, James W.</creator><creatorcontrib>Black, Braydon ; da Silva, Leandro Buffoni Roque ; Hu, Guanggan ; Qu, Xianya ; Smith, Daniel F. Q. ; Magaña, Armando Alcázar ; Horianopoulos, Linda C. ; Caza, Mélissa ; Attarian, Rodgoun ; Foster, Leonard J. ; Casadevall, Arturo ; Kronstad, James W.</creatorcontrib><description>The fungal pathogen
Cryptococcus neoformans
is well adapted to its host environment. It has several defence mechanisms to evade oxidative and nitrosative agents released by phagocytic host cells during infection. Among them, melanin production is linked to both fungal virulence and defence against harmful free radicals that facilitate host innate immunity. How
C.
neoformans
manipulates its redox environment to facilitate melanin formation and virulence is unclear. Here we show that the antioxidant glutathione is inextricably linked to redox-active processes that facilitate melanin and titan cell production, as well as survival in macrophages and virulence in a murine model of cryptococcosis. Comparative metabolomics revealed that disruption of glutathione biosynthesis leads to accumulation of reducing and acidic compounds in the extracellular environment of mutant cells. Overall, these findings highlight the importance of redox homeostasis and metabolic compensation in pathogen adaptation to the host environment and suggest new avenues for antifungal drug development.
Glutathione metabolism in
Cryptococcus neoformans
influences the redox environment and melanin production, and thus affects fungal virulence.</description><identifier>ISSN: 2058-5276</identifier><identifier>EISSN: 2058-5276</identifier><identifier>DOI: 10.1038/s41564-024-01721-x</identifier><identifier>PMID: 38956248</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 13/21 ; 13/31 ; 38/70 ; 38/77 ; 631/208/325 ; 631/326/193/2542 ; 631/326/421 ; Animal models ; Animals ; Biomedical and Life Sciences ; Cryptococcosis ; Cryptococcosis - microbiology ; Cryptococcus neoformans ; Cryptococcus neoformans - genetics ; Cryptococcus neoformans - metabolism ; Cryptococcus neoformans - pathogenicity ; Disease Models, Animal ; Drug development ; Drug metabolism ; Female ; Free radicals ; Gene Expression Regulation, Fungal ; Glutathione ; Glutathione - metabolism ; Homeostasis ; Infectious Diseases ; Innate immunity ; Life Sciences ; Macrophages ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages - microbiology ; Medical Microbiology ; Melanin ; Melanins - biosynthesis ; Melanins - metabolism ; Metabolomics ; Mice ; Microbiology ; Oxidation-Reduction ; Parasitology ; Pathogens ; Phagocytes ; Virology ; Virulence</subject><ispartof>Nature microbiology, 2024-08, Vol.9 (8), p.2084-2098</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Nature Limited.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c256t-f8b01488c0a9b1377f6d3e0da9a98bdc7c1e4db663b0be31bc918314f8e68d6e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38956248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Black, Braydon</creatorcontrib><creatorcontrib>da Silva, Leandro Buffoni Roque</creatorcontrib><creatorcontrib>Hu, Guanggan</creatorcontrib><creatorcontrib>Qu, Xianya</creatorcontrib><creatorcontrib>Smith, Daniel F. Q.</creatorcontrib><creatorcontrib>Magaña, Armando Alcázar</creatorcontrib><creatorcontrib>Horianopoulos, Linda C.</creatorcontrib><creatorcontrib>Caza, Mélissa</creatorcontrib><creatorcontrib>Attarian, Rodgoun</creatorcontrib><creatorcontrib>Foster, Leonard J.</creatorcontrib><creatorcontrib>Casadevall, Arturo</creatorcontrib><creatorcontrib>Kronstad, James W.</creatorcontrib><title>Glutathione-mediated redox regulation in Cryptococcus neoformans impacts virulence</title><title>Nature microbiology</title><addtitle>Nat Microbiol</addtitle><addtitle>Nat Microbiol</addtitle><description>The fungal pathogen
Cryptococcus neoformans
is well adapted to its host environment. It has several defence mechanisms to evade oxidative and nitrosative agents released by phagocytic host cells during infection. Among them, melanin production is linked to both fungal virulence and defence against harmful free radicals that facilitate host innate immunity. How
C.
neoformans
manipulates its redox environment to facilitate melanin formation and virulence is unclear. Here we show that the antioxidant glutathione is inextricably linked to redox-active processes that facilitate melanin and titan cell production, as well as survival in macrophages and virulence in a murine model of cryptococcosis. Comparative metabolomics revealed that disruption of glutathione biosynthesis leads to accumulation of reducing and acidic compounds in the extracellular environment of mutant cells. Overall, these findings highlight the importance of redox homeostasis and metabolic compensation in pathogen adaptation to the host environment and suggest new avenues for antifungal drug development.
Glutathione metabolism in
Cryptococcus neoformans
influences the redox environment and melanin production, and thus affects fungal virulence.</description><subject>13/106</subject><subject>13/21</subject><subject>13/31</subject><subject>38/70</subject><subject>38/77</subject><subject>631/208/325</subject><subject>631/326/193/2542</subject><subject>631/326/421</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Cryptococcosis</subject><subject>Cryptococcosis - microbiology</subject><subject>Cryptococcus neoformans</subject><subject>Cryptococcus neoformans - genetics</subject><subject>Cryptococcus neoformans - metabolism</subject><subject>Cryptococcus neoformans - pathogenicity</subject><subject>Disease Models, Animal</subject><subject>Drug development</subject><subject>Drug metabolism</subject><subject>Female</subject><subject>Free radicals</subject><subject>Gene Expression Regulation, Fungal</subject><subject>Glutathione</subject><subject>Glutathione - metabolism</subject><subject>Homeostasis</subject><subject>Infectious Diseases</subject><subject>Innate immunity</subject><subject>Life Sciences</subject><subject>Macrophages</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - microbiology</subject><subject>Medical Microbiology</subject><subject>Melanin</subject><subject>Melanins - biosynthesis</subject><subject>Melanins - metabolism</subject><subject>Metabolomics</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Oxidation-Reduction</subject><subject>Parasitology</subject><subject>Pathogens</subject><subject>Phagocytes</subject><subject>Virology</subject><subject>Virulence</subject><issn>2058-5276</issn><issn>2058-5276</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKxDAUhoMozjDOC7iQghs31VzaNF3KoKMwIIiuQ5qcjh3apiatzLy90Y4XXLjIBc53_nP4EDol-JJgJq58QlKexJiGQzJK4u0BmlKcijilGT_89Z-gufcbjDHhlHPBj9GEiTzlNBFT9Lish171L5VtIW7AVKoHEzkwdhvu9VCrPpSiqo0Wbtf1VlutBx-1YEvrGtX6qGo6pXsfvVVuqKHVcIKOSlV7mO_fGXq-vXla3MWrh-X94noVa5ryPi5FgUkihMYqLwjLspIbBtioXOWiMDrTBBJTcM4KXAAjhc6JYCQpBXBhOLAZuhhzO2dfB_C9bCqvoa5V2G7wkuEsZRkPbgJ6_gfd2MG1YbtA5RgLkoTsGaIjpZ313kEpO1c1yu0kwfJDuhylyyBdfkqX29B0to8eiuDvu-VLcQDYCPhQatfgfmb_E_sOhqSORA</recordid><startdate>20240801</startdate><enddate>20240801</enddate><creator>Black, Braydon</creator><creator>da Silva, Leandro Buffoni Roque</creator><creator>Hu, Guanggan</creator><creator>Qu, Xianya</creator><creator>Smith, Daniel F. Q.</creator><creator>Magaña, Armando Alcázar</creator><creator>Horianopoulos, Linda C.</creator><creator>Caza, Mélissa</creator><creator>Attarian, Rodgoun</creator><creator>Foster, Leonard J.</creator><creator>Casadevall, Arturo</creator><creator>Kronstad, James W.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7X8</scope></search><sort><creationdate>20240801</creationdate><title>Glutathione-mediated redox regulation in Cryptococcus neoformans impacts virulence</title><author>Black, Braydon ; da Silva, Leandro Buffoni Roque ; Hu, Guanggan ; Qu, Xianya ; Smith, Daniel F. Q. ; Magaña, Armando Alcázar ; Horianopoulos, Linda C. ; Caza, Mélissa ; Attarian, Rodgoun ; Foster, Leonard J. ; Casadevall, Arturo ; Kronstad, James W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c256t-f8b01488c0a9b1377f6d3e0da9a98bdc7c1e4db663b0be31bc918314f8e68d6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>13/106</topic><topic>13/21</topic><topic>13/31</topic><topic>38/70</topic><topic>38/77</topic><topic>631/208/325</topic><topic>631/326/193/2542</topic><topic>631/326/421</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Cryptococcosis</topic><topic>Cryptococcosis - microbiology</topic><topic>Cryptococcus neoformans</topic><topic>Cryptococcus neoformans - genetics</topic><topic>Cryptococcus neoformans - metabolism</topic><topic>Cryptococcus neoformans - pathogenicity</topic><topic>Disease Models, Animal</topic><topic>Drug development</topic><topic>Drug metabolism</topic><topic>Female</topic><topic>Free radicals</topic><topic>Gene Expression Regulation, Fungal</topic><topic>Glutathione</topic><topic>Glutathione - metabolism</topic><topic>Homeostasis</topic><topic>Infectious Diseases</topic><topic>Innate immunity</topic><topic>Life Sciences</topic><topic>Macrophages</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Macrophages - microbiology</topic><topic>Medical Microbiology</topic><topic>Melanin</topic><topic>Melanins - biosynthesis</topic><topic>Melanins - metabolism</topic><topic>Metabolomics</topic><topic>Mice</topic><topic>Microbiology</topic><topic>Oxidation-Reduction</topic><topic>Parasitology</topic><topic>Pathogens</topic><topic>Phagocytes</topic><topic>Virology</topic><topic>Virulence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Black, Braydon</creatorcontrib><creatorcontrib>da Silva, Leandro Buffoni Roque</creatorcontrib><creatorcontrib>Hu, Guanggan</creatorcontrib><creatorcontrib>Qu, Xianya</creatorcontrib><creatorcontrib>Smith, Daniel F. Q.</creatorcontrib><creatorcontrib>Magaña, Armando Alcázar</creatorcontrib><creatorcontrib>Horianopoulos, Linda C.</creatorcontrib><creatorcontrib>Caza, Mélissa</creatorcontrib><creatorcontrib>Attarian, Rodgoun</creatorcontrib><creatorcontrib>Foster, Leonard J.</creatorcontrib><creatorcontrib>Casadevall, Arturo</creatorcontrib><creatorcontrib>Kronstad, James W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nature microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Black, Braydon</au><au>da Silva, Leandro Buffoni Roque</au><au>Hu, Guanggan</au><au>Qu, Xianya</au><au>Smith, Daniel F. Q.</au><au>Magaña, Armando Alcázar</au><au>Horianopoulos, Linda C.</au><au>Caza, Mélissa</au><au>Attarian, Rodgoun</au><au>Foster, Leonard J.</au><au>Casadevall, Arturo</au><au>Kronstad, James W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glutathione-mediated redox regulation in Cryptococcus neoformans impacts virulence</atitle><jtitle>Nature microbiology</jtitle><stitle>Nat Microbiol</stitle><addtitle>Nat Microbiol</addtitle><date>2024-08-01</date><risdate>2024</risdate><volume>9</volume><issue>8</issue><spage>2084</spage><epage>2098</epage><pages>2084-2098</pages><issn>2058-5276</issn><eissn>2058-5276</eissn><abstract>The fungal pathogen
Cryptococcus neoformans
is well adapted to its host environment. It has several defence mechanisms to evade oxidative and nitrosative agents released by phagocytic host cells during infection. Among them, melanin production is linked to both fungal virulence and defence against harmful free radicals that facilitate host innate immunity. How
C.
neoformans
manipulates its redox environment to facilitate melanin formation and virulence is unclear. Here we show that the antioxidant glutathione is inextricably linked to redox-active processes that facilitate melanin and titan cell production, as well as survival in macrophages and virulence in a murine model of cryptococcosis. Comparative metabolomics revealed that disruption of glutathione biosynthesis leads to accumulation of reducing and acidic compounds in the extracellular environment of mutant cells. Overall, these findings highlight the importance of redox homeostasis and metabolic compensation in pathogen adaptation to the host environment and suggest new avenues for antifungal drug development.
Glutathione metabolism in
Cryptococcus neoformans
influences the redox environment and melanin production, and thus affects fungal virulence.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>38956248</pmid><doi>10.1038/s41564-024-01721-x</doi><tpages>15</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2058-5276 |
| ispartof | Nature microbiology, 2024-08, Vol.9 (8), p.2084-2098 |
| issn | 2058-5276 2058-5276 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3075376721 |
| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | 13/106 13/21 13/31 38/70 38/77 631/208/325 631/326/193/2542 631/326/421 Animal models Animals Biomedical and Life Sciences Cryptococcosis Cryptococcosis - microbiology Cryptococcus neoformans Cryptococcus neoformans - genetics Cryptococcus neoformans - metabolism Cryptococcus neoformans - pathogenicity Disease Models, Animal Drug development Drug metabolism Female Free radicals Gene Expression Regulation, Fungal Glutathione Glutathione - metabolism Homeostasis Infectious Diseases Innate immunity Life Sciences Macrophages Macrophages - immunology Macrophages - metabolism Macrophages - microbiology Medical Microbiology Melanin Melanins - biosynthesis Melanins - metabolism Metabolomics Mice Microbiology Oxidation-Reduction Parasitology Pathogens Phagocytes Virology Virulence |
| title | Glutathione-mediated redox regulation in Cryptococcus neoformans impacts virulence |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T20%3A04%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Glutathione-mediated%20redox%20regulation%20in%20Cryptococcus%20neoformans%20impacts%20virulence&rft.jtitle=Nature%20microbiology&rft.au=Black,%20Braydon&rft.date=2024-08-01&rft.volume=9&rft.issue=8&rft.spage=2084&rft.epage=2098&rft.pages=2084-2098&rft.issn=2058-5276&rft.eissn=2058-5276&rft_id=info:doi/10.1038/s41564-024-01721-x&rft_dat=%3Cproquest_cross%3E3090081418%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3090081418&rft_id=info:pmid/38956248&rfr_iscdi=true |