Infection and drug resistance · 2026
A Novel Erg3 T208Is Substitution Associated with Reduced Fluconazole and Voriconazole Susceptibility in Clinical Talaromyces marneffei Isolates from HIV/AIDS Patients.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yanqing Zheng, Xiaofeng Pang, Yinmei Fang, Lida Mo, Xiaolu Luo, Manqi Xiao, Xike Tang
Аннотация
INTRODUCTION: Talaromyces marneffei (T. marneffei) is a life-threatening dimorphic fungus endemic to southern China and Southeast Asia. Decreased triazole susceptibility in T. marneffei has emerged as a major clinical challenge for treating immunocompromised patients, particularly those living with HIV/AIDS. This study aimed to explore the mechanisms underlying reduced susceptibility to fluconazole and voriconazole in T. marneffei isolates derived from HIV/AIDS patients in China.
METHODS: Antifungal susceptibility testing of clinical isolates was performed using the broth microdilution method in accordance with CLSI M27-A4 guidelines. Whole-genome sequencing (WGS) and Sanger sequencing were applied to screen for putative resistance-associated genetic mutations, with a focus on the key ergosterol biosynthesis genes Erg3 and cyp51B. Furthermore, sequence conservation analysis was conducted to evaluate the conservation of candidate mutation sites across pathogenic fungi.
RESULTS: All four clinical isolates exhibited a putative resistance phenotype to fluconazole and voriconazole, with significantly higher minimum inhibitory concentrations (MICs) compared with the wild-type strain. A novel Erg3 c.1195G>A (p.T208I) substitution was identified in three isolates via genomic sequencing. Bioinformatic analysis verified that the T208 residue is highly conserved among T. marneffei and other pathogenic fungi.
CONCLUSION: This is the first study to identify an association between the Erg3 T208I substitution and putative cross-resistance to fluconazole and voriconazole in T. marneffei. The findings of expand the known genetic mechanisms underlying putative antifungal resistance in T. marneffei.
METHODS: Antifungal susceptibility testing of clinical isolates was performed using the broth microdilution method in accordance with CLSI M27-A4 guidelines. Whole-genome sequencing (WGS) and Sanger sequencing were applied to screen for putative resistance-associated genetic mutations, with a focus on the key ergosterol biosynthesis genes Erg3 and cyp51B. Furthermore, sequence conservation analysis was conducted to evaluate the conservation of candidate mutation sites across pathogenic fungi.
RESULTS: All four clinical isolates exhibited a putative resistance phenotype to fluconazole and voriconazole, with significantly higher minimum inhibitory concentrations (MICs) compared with the wild-type strain. A novel Erg3 c.1195G>A (p.T208I) substitution was identified in three isolates via genomic sequencing. Bioinformatic analysis verified that the T208 residue is highly conserved among T. marneffei and other pathogenic fungi.
CONCLUSION: This is the first study to identify an association between the Erg3 T208I substitution and putative cross-resistance to fluconazole and voriconazole in T. marneffei. The findings of expand the known genetic mechanisms underlying putative antifungal resistance in T. marneffei.