Department of Natural Sciences, Lebanese American University, Byblos, Lebanon; Department of Biology, Saint George University of Beirut, Beirut, Lebanon.
Department of Natural Sciences, Lebanese American University, Byblos, Lebanon.
J Glob Antimicrob Resist. 2024 Jun;37:62-68. doi: 10.1016/j.jgar.2024.02.012. Epub 2024 Feb 24.
This study aimed to identify the resistance mechanisms to micafungin and fluconazole in a clinical isolate of Candida glabrata.
The isolate was whole-genome sequenced to identify amino acid changes in key proteins involved in antifungal resistance, and the isolate was further characterised by pathogenicity-related phenotypic assays that supported the sequencing results.
Amino acid substitutions were detected in 8 of 17 protein candidates. Many of these substitutions were novel, including in CHS3, CHS3B, and KRE5, which are involved in the development of micafungin resistance. Regarding fluconazole resistance, overexpression of efflux pumps was observed. Our isolate did not exhibit an increased virulence potential compared with the control strain; however, a significant increase in chitin content and potential to resist the cell surface disruptant sodium dodecyl sulphate was observed.
This clinical Candida glabrata isolate experienced a change in cell wall architecture, which correlates with the development of micafungin resistance.
本研究旨在鉴定临床分离的光滑念珠菌对米卡芬净和氟康唑的耐药机制。
对分离株进行全基因组测序，以鉴定与抗真菌耐药性相关的关键蛋白中的氨基酸变化，并通过与测序结果一致的致病性相关表型检测进一步对分离株进行特征分析。
在 17 个候选蛋白中有 8 个检测到氨基酸取代。其中许多取代是新的，包括在 CHS3、CHS3B 和 KRE5 中，这些基因参与了米卡芬净耐药的发展。关于氟康唑耐药性，观察到外排泵的过度表达。与对照菌株相比，我们的分离株的毒力潜能没有增加；然而，观察到壳聚糖含量的显著增加和对细胞膜破坏剂十二烷基硫酸钠的抗性增加。
该临床光滑念珠菌分离株经历了细胞壁结构的改变，这与米卡芬净耐药的发展相关。
