{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:51:04Z","timestamp":1776689464930,"version":"3.51.2"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Sporotrichosis is a fungal disease caused by a complex of <jats:italic>Sporothrix schenckii<\/jats:italic>, leading to chronic infections of the epidermis and subcutaneous tissue in both humans and animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Through virtual screening targeting the key gene <jats:italic>aba<\/jats:italic>A to screen out the small-molecule drugs to treat Sporotrichosis. To further validate the antifungal activity of small-molecule drugs, growth curves, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) for <jats:italic>Sporothrix globosa<\/jats:italic> (<jats:italic>S. globosa<\/jats:italic>) and <jats:italic>Sporothrix schenckii<\/jats:italic> (<jats:italic>S. schenckii<\/jats:italic>) were measured. In addition, we have done animal experiments to explore the function of the drugs. At the same time, qRT-PCR and transcriptome were used to verify the important role of <jats:italic>aba<\/jats:italic>A gene in <jats:italic>Sporothrix<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Azelastine and Mefloquine effectively inhibit S. globosa and S. schenckii. MBC, and MIC for <jats:italic>S. globosa<\/jats:italic> and <jats:italic>S. schenckii<\/jats:italic> confirmed that both Azelastine and Mefloquine inhibited the growth of <jats:italic>S. globosa<\/jats:italic> and <jats:italic>S. schenckii<\/jats:italic>. Additionally, animal experiments demonstrated that Azelastine and Mefloquine reduced skin lesions in mice; post-treatment observations revealed improvements in inflammatory infiltration and granuloma formation. Through transcriptome analysis and qRT-PCR for validation, our findings demonstrate that the <jats:italic>aba<\/jats:italic>A gene plays a crucial role in regulating the attachment of the <jats:italic>Sporothrix<\/jats:italic> cell wall to the host matrix and in melanin regulation. Notably, when the <jats:italic>aba<\/jats:italic>A gene was inhibited, there was a marked increase in the expression of repair genes. These results emphasize the significance of the <jats:italic>aba<\/jats:italic>A gene in the biology of <jats:italic>Sporothrix<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Two small-molecule drugs exhibit the ability to inhibit <jats:italic>Sporothrix<\/jats:italic> and treat sporotrichosis both in vitro and in murine models, suggesting their potential for development as therapeutic agents for sporotrichosis. And qRT-PCR and transcriptome results underscore the significance of the <jats:italic>aba<\/jats:italic>A gene in <jats:italic>Sporothrix<\/jats:italic>. Our results lay the foundation for the search for new treatments for other mycosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1546020","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T05:25:32Z","timestamp":1745904332000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Screening and transcriptomic analysis of anti-Sporothrix globosa targeting AbaA"],"prefix":"10.3389","volume":"16","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiyuan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chanxu","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangliang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1128\/MCB.14.4.2503","article-title":"The aspergillus Nidulans Abaa gene encodes a transcriptional activator that acts as a genetic switch to control development","volume":"14","author":"Andrianopoulos","year":"1994","journal-title":"Mol. 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