Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hunghom, Hong Kong.
Emerg Microbes Infect. 2022 Dec;11(1):1900-1909. doi: 10.1080/22221751.2022.2098058.
Drug resistance derived from extracellular vesicles (EVs) is an increasingly important research area but has seldom been described regarding fungal pathogens. Here, we characterized EVs derived from a triazole-resistant but amphotericin B-susceptible strain of . Nano- to microgram concentrations of EVs prepared from both broth and solid agar cultures could robustly increase the yeast's survival against both pure and clinical amphotericin B formulations in a dose-dependent manner, resulting in up to 16-fold changes of minimum inhibitory concentration. Meanwhile, this effect was not observed upon addition of these EVs to , nor upon addition of EVs to . No change in susceptibilities was observed upon EV treatment for fluconazole, voriconazole, micafungin, and flucytosine. Mass spectrometry indicated the presence of immunogenic-/drug resistance-implicated proteins in EVs, including alcohol dehydrogenase 1 as well as Mp65-like and Xog1-like proteins in high quantities. Based on these observations, we propose a potential species-specific role for EVs in amphotericin B resistance in . These observations may provide critical insights into treatment of multidrug-resistant .
耐药性来源于细胞外囊泡（EVs）是一个日益重要的研究领域，但很少有关于真菌病原体的描述。在这里，我们对一种唑类耐药但两性霉素 B 敏感的 菌株来源的 EVs 进行了特征描述。从液体和固体琼脂培养物中制备的纳升到微克浓度的 EVs 能够以剂量依赖的方式显著增加酵母对纯两性霉素 B 制剂和临床用两性霉素 B 制剂的生存能力，导致最低抑菌浓度发生高达 16 倍的变化。同时，向 中添加这些 EVs 或向 中添加 EVs 时，不会观察到这种效应。EV 处理对氟康唑、伏立康唑、米卡芬净和氟胞嘧啶的敏感性没有变化。质谱分析表明， EVs 中存在与免疫原性/耐药性相关的蛋白质，包括高丰度的醇脱氢酶 1 以及 Mp65 样和 Xog1 样蛋白。基于这些观察结果，我们提出了 EVs 在 中两性霉素 B 耐药中的潜在种特异性作用。这些观察结果可能为治疗多药耐药 提供重要的见解。
