Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex
Aims The aim of this study was to investigate the mechanisms of action of fisetin, a flavonol with antifungal activity previously evaluated against the Cryptococcus neoformans species complex. Methods and Results Ergosterol content and flow cytometry analysis were determined for the C. neoformans sp...
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| Veröffentlicht in: | Journal of applied microbiology 2016-08, Vol.121 (2), p.373-379 |
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| creator | Reis, M.P.C. Carvalho, C.R.C. Andrade, F.A. Fernandes, O.F.L. Arruda, W. Silva, M.R.R. |
| description | Aims
The aim of this study was to investigate the mechanisms of action of fisetin, a flavonol with antifungal activity previously evaluated against the Cryptococcus neoformans species complex.
Methods and Results
Ergosterol content and flow cytometry analysis were determined for the C. neoformans species complex in the presence of fisetin and ultrastructural analysis of morphology was performed on Cryptococcus gattii and C. neoformans. Decrease in the total cellular ergosterol content after exposure to fisetin ranged from 25·4% after exposure to 128 μg ml−1 to 21·6% after exposure to 64 μg ml−1of fisetin compared with the control (without fisetin). The fisetin effects obtained with flow cytometry showed metabolic impairment, and alterations in its normal morphology caused by fisetin in C. neoformans cells were verified using scanning electron microscopy.
Conclusions
Fisetin is a compound that acts in the biosynthesis of ergosterol. Flow cytometry showed that fisetin reduced viability of the metabolically active cells of C. gattii, while morphological changes explain the action of fisetin in inhibiting growth of these fungi.
Significance and Impact of the Study
This study supports the idea that fisetin may represent a good starting point for the development of future therapeutic substances for cryptococcosis. |
| doi_str_mv | 10.1111/jam.13155 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1808645124</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1808645124</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3865-fd524823e93aed47c2a646cb7fec4205b10ce54e91095221336cd84bc2d1de3d3</originalsourceid><addsrcrecordid>eNqNkc1LwzAYxoMobk4P_gMS8KKHbvludxzD-YHiRQ-eSpa-HRltWpsW3X9vtk4PguAbeBPCj4fn4UHonJIxDTNZ63JMOZXyAA0pVzJiKmaHu7eIJInZAJ14vyaEciLVMRqwmIZfIofobWE9tNZh7bHGdVOV1lu3wtq1Nu_cShdYr8C1YWvrfIvnzaZuK7M9pvPYQZVXTamdx74GY8FjU5V1AZ-n6CjXhYez_T1Cr4ubl_ld9Ph8ez-fPUaGJ8FqnkkmEsZhyjVkIjZMK6HMMs7BiGBxSYkBKWBKyVQyRjlXJkvE0rCMZsAzPkJXvW4w_96Bb9MQwUBR6OCt8ylNSKKEpEz8B5WxoorKgF7-QtdV17gQZEcxwhLOA3XdU6apvG8gT-vGlrrZpJSk22rSUE26qyawF3vFbllC9kN-dxGASQ982AI2fyulD7OnXvIL_SiXVg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1805202833</pqid></control><display><type>article</type><title>Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex</title><source>MEDLINE</source><source>Oxford University Press Journals Current</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Reis, M.P.C. ; Carvalho, C.R.C. ; Andrade, F.A. ; Fernandes, O.F.L. ; Arruda, W. ; Silva, M.R.R.</creator><creatorcontrib>Reis, M.P.C. ; Carvalho, C.R.C. ; Andrade, F.A. ; Fernandes, O.F.L. ; Arruda, W. ; Silva, M.R.R.</creatorcontrib><description>Aims
The aim of this study was to investigate the mechanisms of action of fisetin, a flavonol with antifungal activity previously evaluated against the Cryptococcus neoformans species complex.
Methods and Results
Ergosterol content and flow cytometry analysis were determined for the C. neoformans species complex in the presence of fisetin and ultrastructural analysis of morphology was performed on Cryptococcus gattii and C. neoformans. Decrease in the total cellular ergosterol content after exposure to fisetin ranged from 25·4% after exposure to 128 μg ml−1 to 21·6% after exposure to 64 μg ml−1of fisetin compared with the control (without fisetin). The fisetin effects obtained with flow cytometry showed metabolic impairment, and alterations in its normal morphology caused by fisetin in C. neoformans cells were verified using scanning electron microscopy.
Conclusions
Fisetin is a compound that acts in the biosynthesis of ergosterol. Flow cytometry showed that fisetin reduced viability of the metabolically active cells of C. gattii, while morphological changes explain the action of fisetin in inhibiting growth of these fungi.
Significance and Impact of the Study
This study supports the idea that fisetin may represent a good starting point for the development of future therapeutic substances for cryptococcosis.</description><identifier>ISSN: 1364-5072</identifier><identifier>EISSN: 1365-2672</identifier><identifier>DOI: 10.1111/jam.13155</identifier><identifier>PMID: 27107205</identifier><identifier>CODEN: JAMIFK</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>antifungal activity ; Antifungal Agents - pharmacology ; Biosynthesis ; Cryptococcosis - drug therapy ; Cryptococcosis - parasitology ; Cryptococcus gattii - chemistry ; Cryptococcus gattii - drug effects ; Cryptococcus gattii - growth & development ; Cryptococcus gattii - ultrastructure ; Cryptococcus neoformans ; Cryptococcus neoformans - chemistry ; Cryptococcus neoformans - drug effects ; Cryptococcus neoformans - growth & development ; Cryptococcus neoformans - ultrastructure ; Ergosterol - analysis ; fisetin ; Flavonoids ; Flavonoids - pharmacology ; Fungal infections ; mechanisms of action ; Microbial Sensitivity Tests ; Microbiology ; scanning electron microscopy</subject><ispartof>Journal of applied microbiology, 2016-08, Vol.121 (2), p.373-379</ispartof><rights>2016 The Society for Applied Microbiology</rights><rights>2016 The Society for Applied Microbiology.</rights><rights>Copyright © 2016 The Society for Applied Microbiology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3865-fd524823e93aed47c2a646cb7fec4205b10ce54e91095221336cd84bc2d1de3d3</citedby><cites>FETCH-LOGICAL-c3865-fd524823e93aed47c2a646cb7fec4205b10ce54e91095221336cd84bc2d1de3d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjam.13155$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjam.13155$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27107205$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reis, M.P.C.</creatorcontrib><creatorcontrib>Carvalho, C.R.C.</creatorcontrib><creatorcontrib>Andrade, F.A.</creatorcontrib><creatorcontrib>Fernandes, O.F.L.</creatorcontrib><creatorcontrib>Arruda, W.</creatorcontrib><creatorcontrib>Silva, M.R.R.</creatorcontrib><title>Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex</title><title>Journal of applied microbiology</title><addtitle>J Appl Microbiol</addtitle><description>Aims
The aim of this study was to investigate the mechanisms of action of fisetin, a flavonol with antifungal activity previously evaluated against the Cryptococcus neoformans species complex.
Methods and Results
Ergosterol content and flow cytometry analysis were determined for the C. neoformans species complex in the presence of fisetin and ultrastructural analysis of morphology was performed on Cryptococcus gattii and C. neoformans. Decrease in the total cellular ergosterol content after exposure to fisetin ranged from 25·4% after exposure to 128 μg ml−1 to 21·6% after exposure to 64 μg ml−1of fisetin compared with the control (without fisetin). The fisetin effects obtained with flow cytometry showed metabolic impairment, and alterations in its normal morphology caused by fisetin in C. neoformans cells were verified using scanning electron microscopy.
Conclusions
Fisetin is a compound that acts in the biosynthesis of ergosterol. Flow cytometry showed that fisetin reduced viability of the metabolically active cells of C. gattii, while morphological changes explain the action of fisetin in inhibiting growth of these fungi.
Significance and Impact of the Study
This study supports the idea that fisetin may represent a good starting point for the development of future therapeutic substances for cryptococcosis.</description><subject>antifungal activity</subject><subject>Antifungal Agents - pharmacology</subject><subject>Biosynthesis</subject><subject>Cryptococcosis - drug therapy</subject><subject>Cryptococcosis - parasitology</subject><subject>Cryptococcus gattii - chemistry</subject><subject>Cryptococcus gattii - drug effects</subject><subject>Cryptococcus gattii - growth & development</subject><subject>Cryptococcus gattii - ultrastructure</subject><subject>Cryptococcus neoformans</subject><subject>Cryptococcus neoformans - chemistry</subject><subject>Cryptococcus neoformans - drug effects</subject><subject>Cryptococcus neoformans - growth & development</subject><subject>Cryptococcus neoformans - ultrastructure</subject><subject>Ergosterol - analysis</subject><subject>fisetin</subject><subject>Flavonoids</subject><subject>Flavonoids - pharmacology</subject><subject>Fungal infections</subject><subject>mechanisms of action</subject><subject>Microbial Sensitivity Tests</subject><subject>Microbiology</subject><subject>scanning electron microscopy</subject><issn>1364-5072</issn><issn>1365-2672</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1LwzAYxoMobk4P_gMS8KKHbvludxzD-YHiRQ-eSpa-HRltWpsW3X9vtk4PguAbeBPCj4fn4UHonJIxDTNZ63JMOZXyAA0pVzJiKmaHu7eIJInZAJ14vyaEciLVMRqwmIZfIofobWE9tNZh7bHGdVOV1lu3wtq1Nu_cShdYr8C1YWvrfIvnzaZuK7M9pvPYQZVXTamdx74GY8FjU5V1AZ-n6CjXhYez_T1Cr4ubl_ld9Ph8ez-fPUaGJ8FqnkkmEsZhyjVkIjZMK6HMMs7BiGBxSYkBKWBKyVQyRjlXJkvE0rCMZsAzPkJXvW4w_96Bb9MQwUBR6OCt8ylNSKKEpEz8B5WxoorKgF7-QtdV17gQZEcxwhLOA3XdU6apvG8gT-vGlrrZpJSk22rSUE26qyawF3vFbllC9kN-dxGASQ982AI2fyulD7OnXvIL_SiXVg</recordid><startdate>201608</startdate><enddate>201608</enddate><creator>Reis, M.P.C.</creator><creator>Carvalho, C.R.C.</creator><creator>Andrade, F.A.</creator><creator>Fernandes, O.F.L.</creator><creator>Arruda, W.</creator><creator>Silva, M.R.R.</creator><general>Oxford University Press</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>7QO</scope><scope>7T7</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201608</creationdate><title>Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex</title><author>Reis, M.P.C. ; Carvalho, C.R.C. ; Andrade, F.A. ; Fernandes, O.F.L. ; Arruda, W. ; Silva, M.R.R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3865-fd524823e93aed47c2a646cb7fec4205b10ce54e91095221336cd84bc2d1de3d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>antifungal activity</topic><topic>Antifungal Agents - pharmacology</topic><topic>Biosynthesis</topic><topic>Cryptococcosis - drug therapy</topic><topic>Cryptococcosis - parasitology</topic><topic>Cryptococcus gattii - chemistry</topic><topic>Cryptococcus gattii - drug effects</topic><topic>Cryptococcus gattii - growth & development</topic><topic>Cryptococcus gattii - ultrastructure</topic><topic>Cryptococcus neoformans</topic><topic>Cryptococcus neoformans - chemistry</topic><topic>Cryptococcus neoformans - drug effects</topic><topic>Cryptococcus neoformans - growth & development</topic><topic>Cryptococcus neoformans - ultrastructure</topic><topic>Ergosterol - analysis</topic><topic>fisetin</topic><topic>Flavonoids</topic><topic>Flavonoids - pharmacology</topic><topic>Fungal infections</topic><topic>mechanisms of action</topic><topic>Microbial Sensitivity Tests</topic><topic>Microbiology</topic><topic>scanning electron microscopy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reis, M.P.C.</creatorcontrib><creatorcontrib>Carvalho, C.R.C.</creatorcontrib><creatorcontrib>Andrade, F.A.</creatorcontrib><creatorcontrib>Fernandes, O.F.L.</creatorcontrib><creatorcontrib>Arruda, W.</creatorcontrib><creatorcontrib>Silva, M.R.R.</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>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</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>Journal of applied microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reis, M.P.C.</au><au>Carvalho, C.R.C.</au><au>Andrade, F.A.</au><au>Fernandes, O.F.L.</au><au>Arruda, W.</au><au>Silva, M.R.R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex</atitle><jtitle>Journal of applied microbiology</jtitle><addtitle>J Appl Microbiol</addtitle><date>2016-08</date><risdate>2016</risdate><volume>121</volume><issue>2</issue><spage>373</spage><epage>379</epage><pages>373-379</pages><issn>1364-5072</issn><eissn>1365-2672</eissn><coden>JAMIFK</coden><abstract>Aims
The aim of this study was to investigate the mechanisms of action of fisetin, a flavonol with antifungal activity previously evaluated against the Cryptococcus neoformans species complex.
Methods and Results
Ergosterol content and flow cytometry analysis were determined for the C. neoformans species complex in the presence of fisetin and ultrastructural analysis of morphology was performed on Cryptococcus gattii and C. neoformans. Decrease in the total cellular ergosterol content after exposure to fisetin ranged from 25·4% after exposure to 128 μg ml−1 to 21·6% after exposure to 64 μg ml−1of fisetin compared with the control (without fisetin). The fisetin effects obtained with flow cytometry showed metabolic impairment, and alterations in its normal morphology caused by fisetin in C. neoformans cells were verified using scanning electron microscopy.
Conclusions
Fisetin is a compound that acts in the biosynthesis of ergosterol. Flow cytometry showed that fisetin reduced viability of the metabolically active cells of C. gattii, while morphological changes explain the action of fisetin in inhibiting growth of these fungi.
Significance and Impact of the Study
This study supports the idea that fisetin may represent a good starting point for the development of future therapeutic substances for cryptococcosis.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>27107205</pmid><doi>10.1111/jam.13155</doi><tpages>7</tpages></addata></record> |
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| subjects | antifungal activity Antifungal Agents - pharmacology Biosynthesis Cryptococcosis - drug therapy Cryptococcosis - parasitology Cryptococcus gattii - chemistry Cryptococcus gattii - drug effects Cryptococcus gattii - growth & development Cryptococcus gattii - ultrastructure Cryptococcus neoformans Cryptococcus neoformans - chemistry Cryptococcus neoformans - drug effects Cryptococcus neoformans - growth & development Cryptococcus neoformans - ultrastructure Ergosterol - analysis fisetin Flavonoids Flavonoids - pharmacology Fungal infections mechanisms of action Microbial Sensitivity Tests Microbiology scanning electron microscopy |
| title | Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex |
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