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嗜皮假丝酵母中ADH基因家族的鉴定以及TaADH_like在致病性和氟康唑耐药性中的作用

Identification of the ADH gene family in Trichosporon asahii and the role of TaADH_like in pathogenicity and fluconazole resistance.

作者信息

Liu Zhen, Ma Xiaoping, Zeng Xiangwen, Li Zhiguo, Liu Ruiguo, Luo Rongyan, Wang Weichen, Tahir Muhammad Salman, Wang Chengdong, Gu Yu

机构信息

Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.

China Conservation and Research Center for the Giant Panda, Chengdu, 611800, China.

出版信息

BMC Genomics. 2025 Apr 7;26(1):352. doi: 10.1186/s12864-025-11546-5.

Abstract

Alcohol dehydrogenase has been studied in regulation of fungal growth and development, stress response and pathogenesis, but its function in T. asahii remains unexplored. In this study, we analyzed the ADH gene family in T. asahii for the first time, identifying six ADH genes and containing conserved ADH_N and ADH_Zinc_N domains. We constructed an overexpression strain of the most significantly differentially expressed gene TaADH_like and compared its phenotypes with those of the wild-type strain, focusing on colony morphology, biofilm biomass, stress response, drug resistance, and pathogenicity. The results showed that TaADH_like overexpression reduced sensitivity to hypoxic conditions, altered the hyphae-to-yeast transition, and led to slower growth, decreased colonization ability, reduced tissue damage, and lower lethality. Increased osmotic stress sensitivity and the involvement of the HOG MAPK pathway in the hyphae-to-yeast conversion contributed to the reduced colonization capacity of T. asahii. Furthermore, the overexpression of TaADH_like promoted biofilm formation and led to a slight enhancement in fluconazole resistance in T. asahii. This study is the first to elucidate the function of the alcohol dehydrogenase gene in T. asahii, providing a foundation for future genetic research on this pathogen.

摘要

乙醇脱氢酶已在真菌生长发育、应激反应和致病机制的调控方面得到研究,但其在浅黄曲霉中的功能仍未被探索。在本研究中,我们首次分析了浅黄曲霉中的ADH基因家族,鉴定出六个ADH基因,并含有保守的ADH_N和ADH_Zinc_N结构域。我们构建了差异表达最显著的基因TaADH_like的过表达菌株,并将其表型与野生型菌株进行比较,重点关注菌落形态、生物膜生物量、应激反应、耐药性和致病性。结果表明,TaADH_like过表达降低了对缺氧条件的敏感性,改变了菌丝到酵母的转变,并导致生长缓慢、定殖能力下降、组织损伤减轻和致死率降低。渗透应激敏感性增加以及HOG MAPK途径参与菌丝到酵母的转变导致浅黄曲霉的定殖能力降低。此外,TaADH_like的过表达促进了生物膜形成,并导致浅黄曲霉对氟康唑的耐药性略有增强。本研究首次阐明了乙醇脱氢酶基因在浅黄曲霉中的功能,为该病原菌未来的遗传学研究奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c536/11978018/8400dd9f3c37/12864_2025_11546_Fig1_HTML.jpg

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