Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi
Summary It is estimated that fungal infections, caused most commonly by Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, result in more deaths annually than malaria or tuberculosis. It has long been hypothesized the fungal metabolism plays a critical role in virulence though spec...
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| Veröffentlicht in: | Molecular microbiology 2018-02, Vol.107 (3), p.277-297 |
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| creator | Ries, Laure Nicolas Annick Beattie, Sarah Cramer, Robert A. Goldman, Gustavo H. |
| description | Summary
It is estimated that fungal infections, caused most commonly by Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, result in more deaths annually than malaria or tuberculosis. It has long been hypothesized the fungal metabolism plays a critical role in virulence though specific nutrient sources utilized by human pathogenic fungi in vivo has remained enigmatic. However, the metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche‐dependent manner, is known as carbon catabolite and nitrogen catabolite repression (CCR, NCR), and has been shown to be important for virulence. Several sensory and uptake systems exist, including carbon and nitrogen source‐specific sensors and transporters, that allow scavenging of preferred nutrient sources. Subsequent metabolic utilisation is governed by transcription factors, whose functions and essentiality differ between fungal species. Furthermore, additional factors exist that contribute to the implementation of CCR and NCR. The role of the CCR and NCR‐related factors in virulence varies greatly between fungal species and a substantial gap in knowledge exists regarding specific pathways. Further elucidation of carbon and nitrogen metabolism mechanisms is therefore required in a fungal species‐ and animal model‐specific manner in order to screen for targets that are potential candidates for anti‐fungal drug development.
Fungal infections that result in the death of immunocompromised subjects have risen steadily over the last few years. The metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche‐specific manner, has been shown to be an important virulence determinant. Characterisation of preferred nutrient source utilisation, including sensing and uptake, by pathogenic fungi has only been partially characterised, and further species‐specific elucidation is required, in order to uncover targets for anti‐fungal therapies. |
| doi_str_mv | 10.1111/mmi.13887 |
| format | Article |
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It is estimated that fungal infections, caused most commonly by Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, result in more deaths annually than malaria or tuberculosis. It has long been hypothesized the fungal metabolism plays a critical role in virulence though specific nutrient sources utilized by human pathogenic fungi in vivo has remained enigmatic. However, the metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche‐dependent manner, is known as carbon catabolite and nitrogen catabolite repression (CCR, NCR), and has been shown to be important for virulence. Several sensory and uptake systems exist, including carbon and nitrogen source‐specific sensors and transporters, that allow scavenging of preferred nutrient sources. Subsequent metabolic utilisation is governed by transcription factors, whose functions and essentiality differ between fungal species. Furthermore, additional factors exist that contribute to the implementation of CCR and NCR. The role of the CCR and NCR‐related factors in virulence varies greatly between fungal species and a substantial gap in knowledge exists regarding specific pathways. Further elucidation of carbon and nitrogen metabolism mechanisms is therefore required in a fungal species‐ and animal model‐specific manner in order to screen for targets that are potential candidates for anti‐fungal drug development.
Fungal infections that result in the death of immunocompromised subjects have risen steadily over the last few years. The metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche‐specific manner, has been shown to be an important virulence determinant. Characterisation of preferred nutrient source utilisation, including sensing and uptake, by pathogenic fungi has only been partially characterised, and further species‐specific elucidation is required, in order to uncover targets for anti‐fungal therapies.</description><identifier>ISSN: 0950-382X</identifier><identifier>EISSN: 1365-2958</identifier><identifier>DOI: 10.1111/mmi.13887</identifier><identifier>PMID: 29197127</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Aspergillus fumigatus - metabolism ; Candida albicans - metabolism ; Carbon ; Carbon - metabolism ; Carbon sources ; Catabolite repression ; Catabolite Repression - genetics ; Catabolite Repression - physiology ; Cryptococcus neoformans - metabolism ; Drug development ; Fungal infections ; Fungi ; Fungicides ; Gene Expression Regulation, Fungal - genetics ; Humans ; Malaria ; Metabolism ; Mycoses - metabolism ; Nitrogen ; Nitrogen - metabolism ; Nitrogen sources ; Nutrient sources ; Nutrients ; Species ; Transcription factors ; Transcription Factors - metabolism ; Tropical diseases ; Tuberculosis ; Vector-borne diseases ; Virulence ; Virulence - physiology ; Virulence Factors - metabolism</subject><ispartof>Molecular microbiology, 2018-02, Vol.107 (3), p.277-297</ispartof><rights>2017 John Wiley & Sons Ltd</rights><rights>2017 John Wiley & Sons Ltd.</rights><rights>2018 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5497-26d55a95e265df8b8f45e02b2321d446db5a7b0082ce14283db6dbb1b6cd73d73</citedby><cites>FETCH-LOGICAL-c5497-26d55a95e265df8b8f45e02b2321d446db5a7b0082ce14283db6dbb1b6cd73d73</cites><orcidid>0000-0002-2986-350X</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%2Fmmi.13887$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fmmi.13887$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,777,781,882,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29197127$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ries, Laure Nicolas Annick</creatorcontrib><creatorcontrib>Beattie, Sarah</creatorcontrib><creatorcontrib>Cramer, Robert A.</creatorcontrib><creatorcontrib>Goldman, Gustavo H.</creatorcontrib><title>Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi</title><title>Molecular microbiology</title><addtitle>Mol Microbiol</addtitle><description>Summary
It is estimated that fungal infections, caused most commonly by Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, result in more deaths annually than malaria or tuberculosis. It has long been hypothesized the fungal metabolism plays a critical role in virulence though specific nutrient sources utilized by human pathogenic fungi in vivo has remained enigmatic. However, the metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche‐dependent manner, is known as carbon catabolite and nitrogen catabolite repression (CCR, NCR), and has been shown to be important for virulence. Several sensory and uptake systems exist, including carbon and nitrogen source‐specific sensors and transporters, that allow scavenging of preferred nutrient sources. Subsequent metabolic utilisation is governed by transcription factors, whose functions and essentiality differ between fungal species. Furthermore, additional factors exist that contribute to the implementation of CCR and NCR. The role of the CCR and NCR‐related factors in virulence varies greatly between fungal species and a substantial gap in knowledge exists regarding specific pathways. Further elucidation of carbon and nitrogen metabolism mechanisms is therefore required in a fungal species‐ and animal model‐specific manner in order to screen for targets that are potential candidates for anti‐fungal drug development.
Fungal infections that result in the death of immunocompromised subjects have risen steadily over the last few years. The metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche‐specific manner, has been shown to be an important virulence determinant. Characterisation of preferred nutrient source utilisation, including sensing and uptake, by pathogenic fungi has only been partially characterised, and further species‐specific elucidation is required, in order to uncover targets for anti‐fungal therapies.</description><subject>Aspergillus fumigatus - metabolism</subject><subject>Candida albicans - metabolism</subject><subject>Carbon</subject><subject>Carbon - metabolism</subject><subject>Carbon sources</subject><subject>Catabolite repression</subject><subject>Catabolite Repression - genetics</subject><subject>Catabolite Repression - physiology</subject><subject>Cryptococcus neoformans - metabolism</subject><subject>Drug development</subject><subject>Fungal infections</subject><subject>Fungi</subject><subject>Fungicides</subject><subject>Gene Expression Regulation, Fungal - genetics</subject><subject>Humans</subject><subject>Malaria</subject><subject>Metabolism</subject><subject>Mycoses - metabolism</subject><subject>Nitrogen</subject><subject>Nitrogen - metabolism</subject><subject>Nitrogen sources</subject><subject>Nutrient sources</subject><subject>Nutrients</subject><subject>Species</subject><subject>Transcription factors</subject><subject>Transcription Factors - metabolism</subject><subject>Tropical diseases</subject><subject>Tuberculosis</subject><subject>Vector-borne diseases</subject><subject>Virulence</subject><subject>Virulence - physiology</subject><subject>Virulence Factors - metabolism</subject><issn>0950-382X</issn><issn>1365-2958</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV1rFTEQhoMo9li98A9IwBt7sW2S3XzsjSDFaqGlNwrexSQ7e07KbnJMdk_pvzfr1qKCIZBh5pmXybwIvabklJZzNo7-lNZKySdoQ2vBK9Zy9RRtSMtJVSv27Qi9yPmWEFoTUT9HR6ylraRMbtD3mwOkg4c7HHvsTLIxYBM6HPyU4hZCyU3GxsFPgEdYwzxiH_C0A3zwaR4gOFi6d_NoAt6babc0eof7OWz9S_SsN0OGVw_vMfp68fHL-efq6ubT5fmHq8rxppUVEx3npuXABO96ZVXfcCDMsprRrmlEZ7mRlhDFHNCGqbqzJWepFa6TdbnH6P2qu5_tCJ2DMCUz6H3yo0n3Ohqv_64Ev9PbeNBcSqkEKwLvHgRS_DFDnvTos4NhMAHinPWyMSHapqEFffsPehvnFMr3CqVayZSQC3WyUi7FnBP0j8NQohffdPFN__KtsG_-nP6R_G1UAc5W4M4PcP9_JX19fblK_gT96KPL</recordid><startdate>201802</startdate><enddate>201802</enddate><creator>Ries, Laure Nicolas Annick</creator><creator>Beattie, Sarah</creator><creator>Cramer, Robert A.</creator><creator>Goldman, Gustavo H.</creator><general>Blackwell Publishing Ltd</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</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><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2986-350X</orcidid></search><sort><creationdate>201802</creationdate><title>Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi</title><author>Ries, Laure Nicolas Annick ; Beattie, Sarah ; Cramer, Robert A. ; Goldman, Gustavo H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5497-26d55a95e265df8b8f45e02b2321d446db5a7b0082ce14283db6dbb1b6cd73d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aspergillus fumigatus - metabolism</topic><topic>Candida albicans - metabolism</topic><topic>Carbon</topic><topic>Carbon - metabolism</topic><topic>Carbon sources</topic><topic>Catabolite repression</topic><topic>Catabolite Repression - genetics</topic><topic>Catabolite Repression - physiology</topic><topic>Cryptococcus neoformans - metabolism</topic><topic>Drug development</topic><topic>Fungal infections</topic><topic>Fungi</topic><topic>Fungicides</topic><topic>Gene Expression Regulation, Fungal - genetics</topic><topic>Humans</topic><topic>Malaria</topic><topic>Metabolism</topic><topic>Mycoses - metabolism</topic><topic>Nitrogen</topic><topic>Nitrogen - metabolism</topic><topic>Nitrogen sources</topic><topic>Nutrient sources</topic><topic>Nutrients</topic><topic>Species</topic><topic>Transcription factors</topic><topic>Transcription Factors - metabolism</topic><topic>Tropical diseases</topic><topic>Tuberculosis</topic><topic>Vector-borne diseases</topic><topic>Virulence</topic><topic>Virulence - physiology</topic><topic>Virulence Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ries, Laure Nicolas Annick</creatorcontrib><creatorcontrib>Beattie, Sarah</creatorcontrib><creatorcontrib>Cramer, Robert A.</creatorcontrib><creatorcontrib>Goldman, Gustavo H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids 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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ries, Laure Nicolas Annick</au><au>Beattie, Sarah</au><au>Cramer, Robert A.</au><au>Goldman, Gustavo H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi</atitle><jtitle>Molecular microbiology</jtitle><addtitle>Mol Microbiol</addtitle><date>2018-02</date><risdate>2018</risdate><volume>107</volume><issue>3</issue><spage>277</spage><epage>297</epage><pages>277-297</pages><issn>0950-382X</issn><eissn>1365-2958</eissn><abstract>Summary
It is estimated that fungal infections, caused most commonly by Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, result in more deaths annually than malaria or tuberculosis. It has long been hypothesized the fungal metabolism plays a critical role in virulence though specific nutrient sources utilized by human pathogenic fungi in vivo has remained enigmatic. However, the metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche‐dependent manner, is known as carbon catabolite and nitrogen catabolite repression (CCR, NCR), and has been shown to be important for virulence. Several sensory and uptake systems exist, including carbon and nitrogen source‐specific sensors and transporters, that allow scavenging of preferred nutrient sources. Subsequent metabolic utilisation is governed by transcription factors, whose functions and essentiality differ between fungal species. Furthermore, additional factors exist that contribute to the implementation of CCR and NCR. The role of the CCR and NCR‐related factors in virulence varies greatly between fungal species and a substantial gap in knowledge exists regarding specific pathways. Further elucidation of carbon and nitrogen metabolism mechanisms is therefore required in a fungal species‐ and animal model‐specific manner in order to screen for targets that are potential candidates for anti‐fungal drug development.
Fungal infections that result in the death of immunocompromised subjects have risen steadily over the last few years. The metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche‐specific manner, has been shown to be an important virulence determinant. Characterisation of preferred nutrient source utilisation, including sensing and uptake, by pathogenic fungi has only been partially characterised, and further species‐specific elucidation is required, in order to uncover targets for anti‐fungal therapies.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>29197127</pmid><doi>10.1111/mmi.13887</doi><tpages>21</tpages><orcidid>https://orcid.org/0000-0002-2986-350X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aspergillus fumigatus - metabolism Candida albicans - metabolism Carbon Carbon - metabolism Carbon sources Catabolite repression Catabolite Repression - genetics Catabolite Repression - physiology Cryptococcus neoformans - metabolism Drug development Fungal infections Fungi Fungicides Gene Expression Regulation, Fungal - genetics Humans Malaria Metabolism Mycoses - metabolism Nitrogen Nitrogen - metabolism Nitrogen sources Nutrient sources Nutrients Species Transcription factors Transcription Factors - metabolism Tropical diseases Tuberculosis Vector-borne diseases Virulence Virulence - physiology Virulence Factors - metabolism |
| title | Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi |
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