Hospital infections caused by the opportunistic fungus Candida albicans are increasingly common and life threatening. The first line of defense consists of administering antifungal drugs such as azoles including fluconazole that prevent ergosterol biosynthesis. C. albicans is rapidly developing resistance towards antifungal drugs through various mechanisms including mutations in ERG11 which is a gene involved in the ergosterol biosynthesis pathway. These mutations prevent the binding of the drug and inactivate ergosterol synthesis. Alternatively, upregulation of cell membrane ergosterol content generates resistance by countering the effect of the drug. In this study we sequenced the ERG11 gene in 6 fluconazole sensitive and 8 fluconazole resistant C. albicans isolates recovered from clinical settings in Lebanon and quantified the ergosterol content of their plasma membranes to identify mechanisms linked to fluconazole resistance. A number of pathogenicity attributes were also analyzed to determine any correlation with fluconazole resistance. Our results revealed an increase in ergosterol content in the fluconazole resistant isolates. In addition, we identified both novel and previously reported amino acid substitutions in ERG11 as well as frameshift mutations that might contribute to resistance. The fluconazole resistant isolates did not exhibit an increased virulence potential in a mouse model of systemic infection and showed decreased in vitro potential to form biofilms. No discrepancy between drug resistant and sensitive isolates to cell surface disrupting agents was observed. This approach is the first of its kind to be carried out in Lebanon to identify possible mechanisms and phenotypes of drug resistant C. albicans isolates.

由机会性真菌白色念珠菌引起的医院感染越来越常见并危及生命。第一道防线包括施用抗真菌药物，例如唑类，包括阻止麦角甾醇生物合成的氟康唑。C. albicans正在通过各种机制快速发展对抗真菌药物的抗性，包括ERG11 的突变，ERG11是一种参与麦角甾醇生物合成途径的基因。这些突变阻止了药物的结合并使麦角甾醇合成失活。或者，细胞膜麦角甾醇含量的上调通过抵消药物的作用产生抗性。在这项研究中，我们对ERG11在黎巴嫩临床环境中回收的6 种氟康唑敏感和 8 种氟康唑耐药性白色念珠菌分离株中的基因，并量化其质膜的麦角甾醇含量，以确定与氟康唑耐药性相关的机制。还分析了许多致病性属性以确定与氟康唑耐药性的任何相关性。我们的结果表明，氟康唑耐药菌株中麦角甾醇的含量增加。此外，我们确定了 ERG11 中新的和先前报道的氨基酸替换以及可能导致抗性的移码突变。氟康唑耐药分离株在全身感染小鼠模型中没有表现出增加的毒力潜力，并在体外表现出降低形成生物膜的可能性。没有观察到对细胞表面破坏剂的耐药性和敏感性分离株之间存在差异。这种方法是在黎巴嫩开展的第一个此类方法，用于确定耐药性白色念珠菌分离株的可能机制和表型。