Laboratorio Micología, ICBM - F. de Medicina, Universidad de Chile, Chile.
Clinical Chemistry and Hematology, Hospital del Salvador, Chile.
Rev Iberoam Micol. 2024 Jan-Mar;41(1):7-12. doi: 10.1016/j.riam.2024.04.003. Epub 2024 Sep 19.
Aspergillus fumigatus is a ubiquitous opportunistic pathogen. This fungus can acquire resistance to azole antifungals due to different mutations in the cyp51A gene. Azole resistance has been observed in several continents and appears to be a globally distributed phenomenon. Specific mutations in cyp51A that lead to azole resistance, such as the TR34/L98H modification, have been reported.
To evaluate the azole resistance in clinically isolated A. fumigatus strains.
As a result of our passive surveillance strategy, a total of 23 A. fumigatus isolates from clinical origins were identified through a phylogenetic analysis using the ITS region and β-tubulin gene fragments, and typed with the CSP microsatellite. Azole susceptibility profiles were performed by disk diffusion and microdilution broth methodologies according to CLSI guidelines.
Here we describe, for the first time, the detection of azole-resistant A. fumigatus isolates from clinical origins in Chile with mutations in the cyp51A gene. In addition to the TR34/L98H mutation, one isolate exhibited an F46Y/M172V/E427K-type mutation. Furthermore, microsatellite typing based on cell surface protein (CSP) was performed, showing the t02 (TR34/L98H), t15 (F46Y/M172V/E427K) and t01 (susceptible clinical isolates) genotypes.
Our study demonstrates the presence of mutations related to azole resistance in A. fumigatus strains isolated from clinical samples in Chile. In order to obtain information that may help to tackle the spread of antifungal resistance among A. fumigatus populations, and to ensure the efficacy of future treatments against aspergillosis, a further research is necessary.
烟曲霉是一种无处不在的机会性病原体。由于 cyp51A 基因的不同突变，这种真菌可能会对唑类抗真菌药物产生耐药性。唑类耐药性已在多个大陆观察到，似乎是一种全球分布的现象。已经报道了导致唑类耐药性的 cyp51A 中的特定突变，例如 TR34/L98H 修饰。
评估临床分离的烟曲霉菌株中的唑类耐药性。
由于我们的被动监测策略，通过使用 ITS 区域和β-微管蛋白基因片段进行系统发育分析，共鉴定出 23 株来自临床来源的烟曲霉分离株，并使用 CSP 微卫星进行分型。根据 CLSI 指南，通过圆盘扩散和微量稀释肉汤方法进行唑类药物敏感性分析。
在这里，我们首次描述了在智利从临床来源检测到具有 cyp51A 基因突变的唑类耐药烟曲霉分离株。除了 TR34/L98H 突变外，一个分离株还表现出 F46Y/M172V/E427K 型突变。此外，基于细胞表面蛋白 (CSP) 的微卫星分型显示 t02 (TR34/L98H)、t15 (F46Y/M172V/E427K) 和 t01 (敏感临床分离株) 基因型。
我们的研究表明，在智利从临床样本中分离的烟曲霉菌株中存在与唑类耐药性相关的突变。为了获得可能有助于解决烟曲霉群体中抗真菌药物耐药性传播的信息，并确保未来抗曲霉病治疗的疗效，需要进一步的研究。
