Holotoxin A 1 from Apostichopus japonicus inhibited oropharyngeal and intra-abdominal candidiasis by inducing oxidative damage in Candida albicans
The holotoxin A , isolated from Apostichopus japonicus, exhibits potent antifungal activities, but the mechanism and efficacy against candidiasis are unclear. In this study we have studied the antifungal effects and mechanism of holotoxin A against Candida albicans and in murine oropharyngeal and in...
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| Veröffentlicht in: | British journal of pharmacology 2024-06, Vol.181 (12), p.1857-1873 |
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| container_title | British journal of pharmacology |
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| creator | Liao, Min Xia, Xuekui Meng, Qingzhou Zhu, Chengguang Liao, Binyou Wang, Jiannan Gou, Lichen Zhou, Xuedong Yuan, Wenpeng Cheng, Lei Ren, Biao |
| description | The holotoxin A
, isolated from Apostichopus japonicus, exhibits potent antifungal activities, but the mechanism and efficacy against candidiasis are unclear. In this study we have studied the antifungal effects and mechanism of holotoxin A
against Candida albicans and in murine oropharyngeal and intra-abdominal candidiasis.
The antifungal effect of holotoxin A
against C. albicans was tested in vitro. To explore the antifungal mechanism of holotoxin A
, the transcriptome, ROS levels, and mitochondrial function of C. albicans was evaluated. Effectiveness and systematic toxicity of holotoxin A
in vivo was assessed in the oropharyngeal and intra-abdominal candidiasis models in mice.
Holotoxin A
was a potent fungicide against C. albicans SC5314, clinical strains and drug-resistant strains. Holotoxin A
inhibited oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in C. albicans. Holotoxin A
induced dysfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A
directly inhibited the enzymatic activity of mitochondrial complex I and antagonized with the rotenone, an inhibitor of complex I, against C. albicans. Meanwhile, the complex I subunit NDH51 null mutants showed a decreased susceptibility to holotoxin A
. Furthermore, holotoxin A
significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra-abdominal candidiasis in murine models.
Holotoxin A
is a promising candidate for the development of novel antifungal agents against both oropharyngeal and intra-abdominal candidiasis, especially when caused by drug-resistant strains. |
| doi_str_mv | 10.1111/bph.16333 |
| format | Article |
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, isolated from Apostichopus japonicus, exhibits potent antifungal activities, but the mechanism and efficacy against candidiasis are unclear. In this study we have studied the antifungal effects and mechanism of holotoxin A
against Candida albicans and in murine oropharyngeal and intra-abdominal candidiasis.
The antifungal effect of holotoxin A
against C. albicans was tested in vitro. To explore the antifungal mechanism of holotoxin A
, the transcriptome, ROS levels, and mitochondrial function of C. albicans was evaluated. Effectiveness and systematic toxicity of holotoxin A
in vivo was assessed in the oropharyngeal and intra-abdominal candidiasis models in mice.
Holotoxin A
was a potent fungicide against C. albicans SC5314, clinical strains and drug-resistant strains. Holotoxin A
inhibited oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in C. albicans. Holotoxin A
induced dysfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A
directly inhibited the enzymatic activity of mitochondrial complex I and antagonized with the rotenone, an inhibitor of complex I, against C. albicans. Meanwhile, the complex I subunit NDH51 null mutants showed a decreased susceptibility to holotoxin A
. Furthermore, holotoxin A
significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra-abdominal candidiasis in murine models.
Holotoxin A
is a promising candidate for the development of novel antifungal agents against both oropharyngeal and intra-abdominal candidiasis, especially when caused by drug-resistant strains.</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/bph.16333</identifier><identifier>PMID: 38382564</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Antifungal Agents - pharmacology ; Candida albicans - drug effects ; Candidiasis - drug therapy ; Candidiasis - microbiology ; Candidiasis, Oral - drug therapy ; Candidiasis, Oral - microbiology ; Female ; Intraabdominal Infections - drug therapy ; Intraabdominal Infections - microbiology ; Membrane Potential, Mitochondrial - drug effects ; Mice ; Mice, Inbred BALB C ; Microbial Sensitivity Tests ; Mitochondria - drug effects ; Mitochondria - metabolism ; Oxidative Stress - drug effects ; Reactive Oxygen Species - metabolism ; Stichopus - microbiology</subject><ispartof>British journal of pharmacology, 2024-06, Vol.181 (12), p.1857-1873</ispartof><rights>2024 British Pharmacological Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c574-1d3f13b6a8524db09a4551db30fa9a28da421fd05ce8f946e6644913b555c37e3</cites><orcidid>0000-0002-2762-4740</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38382564$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liao, Min</creatorcontrib><creatorcontrib>Xia, Xuekui</creatorcontrib><creatorcontrib>Meng, Qingzhou</creatorcontrib><creatorcontrib>Zhu, Chengguang</creatorcontrib><creatorcontrib>Liao, Binyou</creatorcontrib><creatorcontrib>Wang, Jiannan</creatorcontrib><creatorcontrib>Gou, Lichen</creatorcontrib><creatorcontrib>Zhou, Xuedong</creatorcontrib><creatorcontrib>Yuan, Wenpeng</creatorcontrib><creatorcontrib>Cheng, Lei</creatorcontrib><creatorcontrib>Ren, Biao</creatorcontrib><title>Holotoxin A 1 from Apostichopus japonicus inhibited oropharyngeal and intra-abdominal candidiasis by inducing oxidative damage in Candida albicans</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>The holotoxin A
, isolated from Apostichopus japonicus, exhibits potent antifungal activities, but the mechanism and efficacy against candidiasis are unclear. In this study we have studied the antifungal effects and mechanism of holotoxin A
against Candida albicans and in murine oropharyngeal and intra-abdominal candidiasis.
The antifungal effect of holotoxin A
against C. albicans was tested in vitro. To explore the antifungal mechanism of holotoxin A
, the transcriptome, ROS levels, and mitochondrial function of C. albicans was evaluated. Effectiveness and systematic toxicity of holotoxin A
in vivo was assessed in the oropharyngeal and intra-abdominal candidiasis models in mice.
Holotoxin A
was a potent fungicide against C. albicans SC5314, clinical strains and drug-resistant strains. Holotoxin A
inhibited oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in C. albicans. Holotoxin A
induced dysfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A
directly inhibited the enzymatic activity of mitochondrial complex I and antagonized with the rotenone, an inhibitor of complex I, against C. albicans. Meanwhile, the complex I subunit NDH51 null mutants showed a decreased susceptibility to holotoxin A
. Furthermore, holotoxin A
significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra-abdominal candidiasis in murine models.
Holotoxin A
is a promising candidate for the development of novel antifungal agents against both oropharyngeal and intra-abdominal candidiasis, especially when caused by drug-resistant strains.</description><subject>Animals</subject><subject>Antifungal Agents - pharmacology</subject><subject>Candida albicans - drug effects</subject><subject>Candidiasis - drug therapy</subject><subject>Candidiasis - microbiology</subject><subject>Candidiasis, Oral - drug therapy</subject><subject>Candidiasis, Oral - microbiology</subject><subject>Female</subject><subject>Intraabdominal Infections - drug therapy</subject><subject>Intraabdominal Infections - microbiology</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microbial Sensitivity Tests</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Oxidative Stress - drug effects</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Stichopus - microbiology</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9UEtOwzAQtRCIlsKCCyBvWaTYsZ04yyoCilSJTffR-JPGVRJHcYroNTgxpgVmM6P3mdE8hO4pWdJYT2poljRjjF2gOeV5lggm6SWaE0LyhFIpZ-gmhD0hkczFNZoxyWQqMj5HX2vf-sl_uh6vMMX16Du8GnyYnG78cAh4D4PvnY6T6xun3GQN9qMfGhiP_c5Ci6E3kZtGSEAZ37k-YjqCzjgILmB1jLQ5aNfvcDxkYHIfFhvoYGcjg8uTFjC0ykVfuEVXNbTB3v32Bdq-PG_LdbJ5f30rV5tEi5wn1LCaMpWBFCk3ihTAhaBGMVJDAak0wFNaGyK0lXXBM5tlnBfRIYTQLLdsgR7Pa_XoQxhtXQ2j6-JXFSXVT6xVjLU6xRq1D2ftcFCdNf_KvxzZN13ydf0</recordid><startdate>202406</startdate><enddate>202406</enddate><creator>Liao, Min</creator><creator>Xia, Xuekui</creator><creator>Meng, Qingzhou</creator><creator>Zhu, Chengguang</creator><creator>Liao, Binyou</creator><creator>Wang, Jiannan</creator><creator>Gou, Lichen</creator><creator>Zhou, Xuedong</creator><creator>Yuan, Wenpeng</creator><creator>Cheng, Lei</creator><creator>Ren, Biao</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-2762-4740</orcidid></search><sort><creationdate>202406</creationdate><title>Holotoxin A 1 from Apostichopus japonicus inhibited oropharyngeal and intra-abdominal candidiasis by inducing oxidative damage in Candida albicans</title><author>Liao, Min ; Xia, Xuekui ; Meng, Qingzhou ; Zhu, Chengguang ; Liao, Binyou ; Wang, Jiannan ; Gou, Lichen ; Zhou, Xuedong ; Yuan, Wenpeng ; Cheng, Lei ; Ren, Biao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c574-1d3f13b6a8524db09a4551db30fa9a28da421fd05ce8f946e6644913b555c37e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Antifungal Agents - pharmacology</topic><topic>Candida albicans - drug effects</topic><topic>Candidiasis - drug therapy</topic><topic>Candidiasis - microbiology</topic><topic>Candidiasis, Oral - drug therapy</topic><topic>Candidiasis, Oral - microbiology</topic><topic>Female</topic><topic>Intraabdominal Infections - drug therapy</topic><topic>Intraabdominal Infections - microbiology</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microbial Sensitivity Tests</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Oxidative Stress - drug effects</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Stichopus - microbiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liao, Min</creatorcontrib><creatorcontrib>Xia, Xuekui</creatorcontrib><creatorcontrib>Meng, Qingzhou</creatorcontrib><creatorcontrib>Zhu, Chengguang</creatorcontrib><creatorcontrib>Liao, Binyou</creatorcontrib><creatorcontrib>Wang, Jiannan</creatorcontrib><creatorcontrib>Gou, Lichen</creatorcontrib><creatorcontrib>Zhou, Xuedong</creatorcontrib><creatorcontrib>Yuan, Wenpeng</creatorcontrib><creatorcontrib>Cheng, Lei</creatorcontrib><creatorcontrib>Ren, Biao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liao, Min</au><au>Xia, Xuekui</au><au>Meng, Qingzhou</au><au>Zhu, Chengguang</au><au>Liao, Binyou</au><au>Wang, Jiannan</au><au>Gou, Lichen</au><au>Zhou, Xuedong</au><au>Yuan, Wenpeng</au><au>Cheng, Lei</au><au>Ren, Biao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Holotoxin A 1 from Apostichopus japonicus inhibited oropharyngeal and intra-abdominal candidiasis by inducing oxidative damage in Candida albicans</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2024-06</date><risdate>2024</risdate><volume>181</volume><issue>12</issue><spage>1857</spage><epage>1873</epage><pages>1857-1873</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><abstract>The holotoxin A
, isolated from Apostichopus japonicus, exhibits potent antifungal activities, but the mechanism and efficacy against candidiasis are unclear. In this study we have studied the antifungal effects and mechanism of holotoxin A
against Candida albicans and in murine oropharyngeal and intra-abdominal candidiasis.
The antifungal effect of holotoxin A
against C. albicans was tested in vitro. To explore the antifungal mechanism of holotoxin A
, the transcriptome, ROS levels, and mitochondrial function of C. albicans was evaluated. Effectiveness and systematic toxicity of holotoxin A
in vivo was assessed in the oropharyngeal and intra-abdominal candidiasis models in mice.
Holotoxin A
was a potent fungicide against C. albicans SC5314, clinical strains and drug-resistant strains. Holotoxin A
inhibited oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in C. albicans. Holotoxin A
induced dysfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A
directly inhibited the enzymatic activity of mitochondrial complex I and antagonized with the rotenone, an inhibitor of complex I, against C. albicans. Meanwhile, the complex I subunit NDH51 null mutants showed a decreased susceptibility to holotoxin A
. Furthermore, holotoxin A
significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra-abdominal candidiasis in murine models.
Holotoxin A
is a promising candidate for the development of novel antifungal agents against both oropharyngeal and intra-abdominal candidiasis, especially when caused by drug-resistant strains.</abstract><cop>England</cop><pmid>38382564</pmid><doi>10.1111/bph.16333</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-2762-4740</orcidid></addata></record> |
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| source | Wiley-Blackwell Journals; MEDLINE |
| subjects | Animals Antifungal Agents - pharmacology Candida albicans - drug effects Candidiasis - drug therapy Candidiasis - microbiology Candidiasis, Oral - drug therapy Candidiasis, Oral - microbiology Female Intraabdominal Infections - drug therapy Intraabdominal Infections - microbiology Membrane Potential, Mitochondrial - drug effects Mice Mice, Inbred BALB C Microbial Sensitivity Tests Mitochondria - drug effects Mitochondria - metabolism Oxidative Stress - drug effects Reactive Oxygen Species - metabolism Stichopus - microbiology |
| title | Holotoxin A 1 from Apostichopus japonicus inhibited oropharyngeal and intra-abdominal candidiasis by inducing oxidative damage in Candida albicans |
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