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In this study we have studied the antifungal effects and mechanism of holotoxin A\n 1<\/jats:sub>\n against\n \n Candida albicans<\/jats:italic>\n <\/jats:styled-content>\n and in murine oropharyngeal and intra\u2010abdominal candidiasis.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n The antifungal effect of holotoxin A\n 1<\/jats:sub>\n against\n \n C. albicans<\/jats:italic>\n <\/jats:styled-content>\n was tested in vitro. To explore the antifungal mechanism of holotoxin A\n 1<\/jats:sub>\n , the transcriptome, ROS levels, and mitochondrial function of\n \n C. albicans<\/jats:italic>\n <\/jats:styled-content>\n was evaluated. Effectiveness and systematic toxicity of holotoxin A\n 1<\/jats:sub>\n in vivo was assessed in the oropharyngeal and intra\u2010abdominal candidiasis models in mice.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n Holotoxin A\n 1<\/jats:sub>\n was a potent fungicide against\n \n C. albicans<\/jats:italic>\n <\/jats:styled-content>\n SC5314, clinical strains and drug\u2010resistant strains. Holotoxin A\n 1<\/jats:sub>\n inhibited oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in\n \n C. albicans<\/jats:italic>\n <\/jats:styled-content>\n . Holotoxin A\n 1<\/jats:sub>\n induced dysfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A\n 1<\/jats:sub>\n directly inhibited the enzymatic activity of mitochondrial complex I and antagonized with the rotenone, an inhibitor of\u00a0complex I, against\n \n C. albicans<\/jats:italic>\n <\/jats:styled-content>\n . Meanwhile, the complex I subunit\n NDH51<\/jats:italic>\n null mutants showed a decreased susceptibility to holotoxin A\n 1<\/jats:sub>\n . Furthermore, holotoxin A\n 1<\/jats:sub>\n significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra\u2010abdominal candidiasis in murine models.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Implications<\/jats:title>\n \n Holotoxin A\n 1<\/jats:sub>\n is a promising candidate for the development of novel antifungal agents against both oropharyngeal and intra\u2010abdominal candidiasis, especially when caused by drug\u2010resistant strains.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.16333","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T18:55:15Z","timestamp":1708541715000},"page":"1857-1873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Holotoxin A\n 1<\/sub>\n from\n \n Apostichopus japonicus<\/i>\n <\/scp>\n inhibited oropharyngeal and intra\u2010abdominal candidiasis by inducing oxidative damage in\n \n Candida albicans<\/i>\n <\/scp>"],"prefix":"10.1111","volume":"181","author":[{"given":"Min","family":"Liao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology Sichuan University Chengdu China"},{"name":"Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology Sichuan University Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuekui","family":"Xia","sequence":"additional","affiliation":[{"name":"Biology Institute, Key Laboratory of Bio\u2010manufacturing of Shandong Province Qilu University of Technology (Shandong Academy of Sciences) Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingzhou","family":"Meng","sequence":"additional","affiliation":[{"name":"Biology Institute, Key Laboratory of Bio\u2010manufacturing of Shandong Province Qilu University of Technology (Shandong Academy 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