High molecular weight chitosan oligosaccharide exhibited antifungal activity by misleading cell wall organization via targeting PHR transglucosidases
The fungal cell wall is an ideal target for the design of antifungal drugs. In this study we used an analog of cell wall polymer, a highly deacetylated high molecular-weight chitosan oligosaccharide (HCOS), to test its effect against pathogenic Candida strains. Results showed that HCOS was successfu...
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| Veröffentlicht in: | Carbohydrate polymers 2022-06, Vol.285, p.119253-119253, Article 119253 |
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| container_title | Carbohydrate polymers |
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| creator | Li, Ruilian Zhu, Limeng Liu, Dongdong Wang, Wenjing Zhang, Chen Jiao, Siming Wei, Jinhua Ren, Lishi Zhang, Yuchen Gou, Xun Yuan, Xianghua Du, Yuguang Wang, Zhuo A. |
| description | The fungal cell wall is an ideal target for the design of antifungal drugs. In this study we used an analog of cell wall polymer, a highly deacetylated high molecular-weight chitosan oligosaccharide (HCOS), to test its effect against pathogenic Candida strains. Results showed that HCOS was successfully incorporated into the dynamic cell wall organization process and exhibited an apparent antifungal activity against both plankton and mature fungal biofilm, by impairing the cell wall integrity. Unexpectedly, mechanistic studies suggested that HCOS exerts its activity by interfering with family members of PHR β-(1,3)-glucanosyl transferases and affecting the connection and assembly of cell wall polysaccharides. Furthermore, HCOS showed great synergistic activity with different fungicides against Candida cells, especially those in biofilm. These findings indicated HCOS has a great potential as an antifungal drug or drug synergist and proposed a novel antifungal strategy with structure-specific oligosaccharides mimicking cell wall polysaccharide fragments.
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| doi_str_mv | 10.1016/j.carbpol.2022.119253 |
| format | Article |
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[Display omitted]</description><identifier>ISSN: 0144-8617</identifier><identifier>EISSN: 1879-1344</identifier><identifier>DOI: 10.1016/j.carbpol.2022.119253</identifier><identifier>PMID: 35287867</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Antifungal Agents - pharmacology ; Biofilm ; Biofilms ; Candida albicans ; Cell Wall ; Chitosan - pharmacology ; Chitosan oligosaccharide ; Microbial Sensitivity Tests ; Molecular Weight ; Oligosaccharides - pharmacology ; PHR transglucosidases</subject><ispartof>Carbohydrate polymers, 2022-06, Vol.285, p.119253-119253, Article 119253</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright © 2022 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-d73b87e722a9b51fcf41107ae526e922e3e2d117c50a4aaa116492677f36abc73</citedby><cites>FETCH-LOGICAL-c412t-d73b87e722a9b51fcf41107ae526e922e3e2d117c50a4aaa116492677f36abc73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.carbpol.2022.119253$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35287867$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Ruilian</creatorcontrib><creatorcontrib>Zhu, Limeng</creatorcontrib><creatorcontrib>Liu, Dongdong</creatorcontrib><creatorcontrib>Wang, Wenjing</creatorcontrib><creatorcontrib>Zhang, Chen</creatorcontrib><creatorcontrib>Jiao, Siming</creatorcontrib><creatorcontrib>Wei, Jinhua</creatorcontrib><creatorcontrib>Ren, Lishi</creatorcontrib><creatorcontrib>Zhang, Yuchen</creatorcontrib><creatorcontrib>Gou, Xun</creatorcontrib><creatorcontrib>Yuan, Xianghua</creatorcontrib><creatorcontrib>Du, Yuguang</creatorcontrib><creatorcontrib>Wang, Zhuo A.</creatorcontrib><title>High molecular weight chitosan oligosaccharide exhibited antifungal activity by misleading cell wall organization via targeting PHR transglucosidases</title><title>Carbohydrate polymers</title><addtitle>Carbohydr Polym</addtitle><description>The fungal cell wall is an ideal target for the design of antifungal drugs. In this study we used an analog of cell wall polymer, a highly deacetylated high molecular-weight chitosan oligosaccharide (HCOS), to test its effect against pathogenic Candida strains. Results showed that HCOS was successfully incorporated into the dynamic cell wall organization process and exhibited an apparent antifungal activity against both plankton and mature fungal biofilm, by impairing the cell wall integrity. Unexpectedly, mechanistic studies suggested that HCOS exerts its activity by interfering with family members of PHR β-(1,3)-glucanosyl transferases and affecting the connection and assembly of cell wall polysaccharides. Furthermore, HCOS showed great synergistic activity with different fungicides against Candida cells, especially those in biofilm. These findings indicated HCOS has a great potential as an antifungal drug or drug synergist and proposed a novel antifungal strategy with structure-specific oligosaccharides mimicking cell wall polysaccharide fragments.
[Display omitted]</description><subject>Antifungal Agents - pharmacology</subject><subject>Biofilm</subject><subject>Biofilms</subject><subject>Candida albicans</subject><subject>Cell Wall</subject><subject>Chitosan - pharmacology</subject><subject>Chitosan oligosaccharide</subject><subject>Microbial Sensitivity Tests</subject><subject>Molecular Weight</subject><subject>Oligosaccharides - pharmacology</subject><subject>PHR transglucosidases</subject><issn>0144-8617</issn><issn>1879-1344</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2O0zAQgC0EYsvCI4B85JIS20mcnBBaAUVaCYTgbE2cSTqVGxfb6VLeg_fFVQtXfBh7pG9-rI-xl6Jci1I0b3ZrC6E_eLeWpZRrITpZq0dsJVrdFUJV1WO2KkVVFW0j9A17FuOuzKcR5VN2o2rZ6rbRK_Z7Q9OW771DuzgI_AFznrjdUvIRZu4dTflh7RYCDcjx55Z6SjhwmBONyzyB42ATHSmdeH_ie4oOYaB54had4w-Qgw8TzPQLEvmZHwl4gjBhOkNfNl95CjDHyS3WRxogYnzOnozgIr643rfs-4f33-42xf3nj5_u3t0XthIyFYNWfatRSwldX4vRjpUQpQasZYOdlKhQDkJoW5dQAYAQTdXJRutRNdBbrW7Z60vfQ_A_FozJ5PXPa8OMfolGNiq3UaqqM1pfUBt8jAFHcwi0h3AyojRnI2ZnrkbM2Yi5GMl1r64jln6Pw7-qvwoy8PYCYP7okTCYaAlniwMFtMkMnv4z4g-AP6M8</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Li, Ruilian</creator><creator>Zhu, Limeng</creator><creator>Liu, Dongdong</creator><creator>Wang, Wenjing</creator><creator>Zhang, Chen</creator><creator>Jiao, Siming</creator><creator>Wei, Jinhua</creator><creator>Ren, Lishi</creator><creator>Zhang, Yuchen</creator><creator>Gou, Xun</creator><creator>Yuan, Xianghua</creator><creator>Du, Yuguang</creator><creator>Wang, Zhuo A.</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>20220601</creationdate><title>High molecular weight chitosan oligosaccharide exhibited antifungal activity by misleading cell wall organization via targeting PHR transglucosidases</title><author>Li, Ruilian ; Zhu, Limeng ; Liu, Dongdong ; Wang, Wenjing ; Zhang, Chen ; Jiao, Siming ; Wei, Jinhua ; Ren, Lishi ; Zhang, Yuchen ; Gou, Xun ; Yuan, Xianghua ; Du, Yuguang ; Wang, Zhuo A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-d73b87e722a9b51fcf41107ae526e922e3e2d117c50a4aaa116492677f36abc73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antifungal Agents - pharmacology</topic><topic>Biofilm</topic><topic>Biofilms</topic><topic>Candida albicans</topic><topic>Cell Wall</topic><topic>Chitosan - pharmacology</topic><topic>Chitosan oligosaccharide</topic><topic>Microbial Sensitivity Tests</topic><topic>Molecular Weight</topic><topic>Oligosaccharides - pharmacology</topic><topic>PHR transglucosidases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Ruilian</creatorcontrib><creatorcontrib>Zhu, Limeng</creatorcontrib><creatorcontrib>Liu, Dongdong</creatorcontrib><creatorcontrib>Wang, Wenjing</creatorcontrib><creatorcontrib>Zhang, Chen</creatorcontrib><creatorcontrib>Jiao, Siming</creatorcontrib><creatorcontrib>Wei, Jinhua</creatorcontrib><creatorcontrib>Ren, Lishi</creatorcontrib><creatorcontrib>Zhang, Yuchen</creatorcontrib><creatorcontrib>Gou, Xun</creatorcontrib><creatorcontrib>Yuan, Xianghua</creatorcontrib><creatorcontrib>Du, Yuguang</creatorcontrib><creatorcontrib>Wang, Zhuo A.</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>Carbohydrate polymers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Ruilian</au><au>Zhu, Limeng</au><au>Liu, Dongdong</au><au>Wang, Wenjing</au><au>Zhang, Chen</au><au>Jiao, Siming</au><au>Wei, Jinhua</au><au>Ren, Lishi</au><au>Zhang, Yuchen</au><au>Gou, Xun</au><au>Yuan, Xianghua</au><au>Du, Yuguang</au><au>Wang, Zhuo A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High molecular weight chitosan oligosaccharide exhibited antifungal activity by misleading cell wall organization via targeting PHR transglucosidases</atitle><jtitle>Carbohydrate polymers</jtitle><addtitle>Carbohydr Polym</addtitle><date>2022-06-01</date><risdate>2022</risdate><volume>285</volume><spage>119253</spage><epage>119253</epage><pages>119253-119253</pages><artnum>119253</artnum><issn>0144-8617</issn><eissn>1879-1344</eissn><abstract>The fungal cell wall is an ideal target for the design of antifungal drugs. In this study we used an analog of cell wall polymer, a highly deacetylated high molecular-weight chitosan oligosaccharide (HCOS), to test its effect against pathogenic Candida strains. Results showed that HCOS was successfully incorporated into the dynamic cell wall organization process and exhibited an apparent antifungal activity against both plankton and mature fungal biofilm, by impairing the cell wall integrity. Unexpectedly, mechanistic studies suggested that HCOS exerts its activity by interfering with family members of PHR β-(1,3)-glucanosyl transferases and affecting the connection and assembly of cell wall polysaccharides. Furthermore, HCOS showed great synergistic activity with different fungicides against Candida cells, especially those in biofilm. These findings indicated HCOS has a great potential as an antifungal drug or drug synergist and proposed a novel antifungal strategy with structure-specific oligosaccharides mimicking cell wall polysaccharide fragments.
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| subjects | Antifungal Agents - pharmacology Biofilm Biofilms Candida albicans Cell Wall Chitosan - pharmacology Chitosan oligosaccharide Microbial Sensitivity Tests Molecular Weight Oligosaccharides - pharmacology PHR transglucosidases |
| title | High molecular weight chitosan oligosaccharide exhibited antifungal activity by misleading cell wall organization via targeting PHR transglucosidases |
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