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Cryptococcus neoformans is a global health threat that frequently causes life-threatening meningitis and fungemia, particularly in immunocompromised patients. In this study, we identify a novel anti-C. neoformans peptide, QS18 (QCFKVCFRKRCFTKCSRS), from the venom gland of China\u2019s native spider species Chilobrachys liboensis by utilizing bioinformatic tools. QS18 shares over 50% sequence similarity with tachyplesin peptides, previously identified only in horseshoe crab hemocytes, expanding the known repertoire of the tachyplesin family to terrestrial arachnids. The oxidative folding of QS18 notably enhances its antifungal activity and stability, resulting in a minimum inhibitory concentration of 1.4 \u00b5M. The antimicrobial mechanism of QS18 involves cell membrane disruption. QS18 exhibits less than 5% hemolysis in human erythrocytes, indicating microbial selectivity and a favorable safety profile for therapeutic use. Furthermore, mouse model studies highlight QS18\u2019s ability as an antifungal agent with notable anti-inflammatory activity. Our study demonstrates QS18 as both a promising template for spider venom peptide research and a novel candidate for the development of peptide antifungals.<\/jats:p>","DOI":"10.3390\/microorganisms12122648","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T06:44:33Z","timestamp":1734677073000},"page":"2648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Tachyplesin Antimicrobial Peptide from Theraphosidae Spiders with Potent Antifungal Activity Against Cryptococcus neoformans"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1815-5303","authenticated-orcid":false,"given":"Brenda B.","family":"Michira","sequence":"first","affiliation":[{"name":"Key Laboratory of Genetic Evolution & Animal Models, Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650201, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Mwangi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Genetic Evolution & Animal Models, Engineering Laboratory of Peptides of Chinese Academy of Sciences, 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Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650201, China"},{"name":"Medical College of Tianjin University, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demeke","family":"Asmamaw","sequence":"additional","affiliation":[{"name":"Key Laboratory of Genetic Evolution & Animal Models, Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650201, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-2760","authenticated-orcid":false,"given":"Dawit Adisu","family":"Tadese","sequence":"additional","affiliation":[{"name":"Key Laboratory of Genetic Evolution & Animal Models, Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650201, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinai","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Genetic Evolution & Animal Models, Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, and Sino-African Joint Research Center, New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650201, China"},{"name":"School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehwish","family":"Khalid","sequence":"additional","affiliation":[{"name":"Key Laboratory of Genetic Evolution & Animal Models, Engineering Laboratory of Peptides of Chinese 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105521","DOI":"10.1016\/j.micpath.2022.105521","article-title":"A holistic review on Cryptococcus neoformans","volume":"166","author":"Rathore","year":"2022","journal-title":"Microb. 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