Cell wall melanin impedes growth of the Cryptococcus neoformans polysaccharide capsule by sequestering calcium
has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of within the human host, the two most prominent of which are the polysacchari...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2024-09, Vol.121 (38), p.e2412534121 |
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creator | Baker, Rosanna P Liu, Amy Z Casadevall, Arturo |
description | has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of
within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response. |
doi_str_mv | 10.1073/pnas.2412534121 |
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within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response.</description><identifier>ISSN: 0027-8424</identifier><identifier>ISSN: 1091-6490</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2412534121</identifier><identifier>PMID: 39259590</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Bridge maintenance ; Calcium ; Calcium - metabolism ; Cell culture ; Cell Wall - metabolism ; Cell walls ; Competitive materials ; Cryptococcus neoformans ; Cryptococcus neoformans - growth & development ; Cryptococcus neoformans - metabolism ; Fungal Capsules - metabolism ; Fungal Polysaccharides - metabolism ; Fungi ; Humans ; Immune response ; Immune system ; Melanin ; Melanins - metabolism ; Polysaccharides ; Polysaccharides - metabolism ; Sequestering ; Thickness ; Virulence ; Virulence factors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2024-09, Vol.121 (38), p.e2412534121</ispartof><rights>Copyright National Academy of Sciences Sep 17, 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1651-6e090e66932191f4e0a6324073824a833d4195752d2a9a50079802df684f07133</cites><orcidid>0000-0002-9970-6278 ; 0000-0002-9402-9167</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39259590$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baker, Rosanna P</creatorcontrib><creatorcontrib>Liu, Amy Z</creatorcontrib><creatorcontrib>Casadevall, Arturo</creatorcontrib><title>Cell wall melanin impedes growth of the Cryptococcus neoformans polysaccharide capsule by sequestering calcium</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of
within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response.</description><subject>Bridge maintenance</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Cell culture</subject><subject>Cell Wall - metabolism</subject><subject>Cell walls</subject><subject>Competitive materials</subject><subject>Cryptococcus neoformans</subject><subject>Cryptococcus neoformans - growth & development</subject><subject>Cryptococcus neoformans - metabolism</subject><subject>Fungal Capsules - metabolism</subject><subject>Fungal Polysaccharides - metabolism</subject><subject>Fungi</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Melanin</subject><subject>Melanins - metabolism</subject><subject>Polysaccharides</subject><subject>Polysaccharides - metabolism</subject><subject>Sequestering</subject><subject>Thickness</subject><subject>Virulence</subject><subject>Virulence factors</subject><issn>0027-8424</issn><issn>1091-6490</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctLxDAQxoMo7vo4e5OAFy-7ziRpmxyl-IIFL3ouMZ26lbapyRbZ_974Bi8zMPxm-L75GDtBWCIU8mIcbFwKhSKTqeAOmyMYXOTKwC6bA4hioZVQM3YQ4wsAmEzDPptJIzKTGZizoaSu4282lZ46O7QDb_uRaor8Ofi3zZr7hm_WxMuwHTfeeeemyAfyjQ-9HSIffbeN1rm1DW1N3NkxTh3xpy2P9DpR3FBoh-c071w79Udsr7FdpOPvfsger68eytvF6v7mrrxcLRzmWdJPYIDy3EiBBhtFYHMpVHKshbJaylqhyYpM1MIamwEURoOom1yrBgqU8pCdf90dg_9UUfVtdMmqTdKnWEkEoTWiEAk9-4e--CkMSV2iUBhUhYZEXXxRLvgYAzXVGNrehm2FUH1EUX1EUf1FkTZOv-9OTz3Vv_zP7-U7E5uD5g</recordid><startdate>20240917</startdate><enddate>20240917</enddate><creator>Baker, Rosanna P</creator><creator>Liu, Amy Z</creator><creator>Casadevall, Arturo</creator><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9970-6278</orcidid><orcidid>https://orcid.org/0000-0002-9402-9167</orcidid></search><sort><creationdate>20240917</creationdate><title>Cell wall melanin impedes growth of the Cryptococcus neoformans polysaccharide capsule by sequestering calcium</title><author>Baker, Rosanna P ; Liu, Amy Z ; Casadevall, Arturo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1651-6e090e66932191f4e0a6324073824a833d4195752d2a9a50079802df684f07133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Bridge maintenance</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>Cell culture</topic><topic>Cell Wall - metabolism</topic><topic>Cell walls</topic><topic>Competitive materials</topic><topic>Cryptococcus neoformans</topic><topic>Cryptococcus neoformans - growth & development</topic><topic>Cryptococcus neoformans - metabolism</topic><topic>Fungal Capsules - metabolism</topic><topic>Fungal Polysaccharides - metabolism</topic><topic>Fungi</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Melanin</topic><topic>Melanins - metabolism</topic><topic>Polysaccharides</topic><topic>Polysaccharides - metabolism</topic><topic>Sequestering</topic><topic>Thickness</topic><topic>Virulence</topic><topic>Virulence factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baker, Rosanna P</creatorcontrib><creatorcontrib>Liu, Amy Z</creatorcontrib><creatorcontrib>Casadevall, Arturo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baker, Rosanna P</au><au>Liu, Amy Z</au><au>Casadevall, Arturo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cell wall melanin impedes growth of the Cryptococcus neoformans polysaccharide capsule by sequestering calcium</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2024-09-17</date><risdate>2024</risdate><volume>121</volume><issue>38</issue><spage>e2412534121</spage><pages>e2412534121-</pages><issn>0027-8424</issn><issn>1091-6490</issn><eissn>1091-6490</eissn><abstract>has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of
within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>39259590</pmid><doi>10.1073/pnas.2412534121</doi><orcidid>https://orcid.org/0000-0002-9970-6278</orcidid><orcidid>https://orcid.org/0000-0002-9402-9167</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Bridge maintenance Calcium Calcium - metabolism Cell culture Cell Wall - metabolism Cell walls Competitive materials Cryptococcus neoformans Cryptococcus neoformans - growth & development Cryptococcus neoformans - metabolism Fungal Capsules - metabolism Fungal Polysaccharides - metabolism Fungi Humans Immune response Immune system Melanin Melanins - metabolism Polysaccharides Polysaccharides - metabolism Sequestering Thickness Virulence Virulence factors |
title | Cell wall melanin impedes growth of the Cryptococcus neoformans polysaccharide capsule by sequestering calcium |
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