Eliaš Daniel, Tóth Hervay Nora, Černáková Lucia, Gbelská Yvetta
Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 842 15 Bratislava, Slovakia.
J Fungi (Basel). 2024 Sep 26;10(10):669. doi: 10.3390/jof10100669.
The gene encodes the sterol C24-methyltransferase converting zymosterol to fecosterol in the ergosterol biosynthetic pathway. Here, we extend the results of functional analysis of the gene, which was previously shown to modulate drug susceptibility in mutant cells, by demonstrating that its deletion leads to increased susceptibility to cycloheximide, 4-nitroquinoline-N-oxide and weak organic acids, and such effects are associated with attenuated virulence. Together with abrogated efflux of drug substrates by Cdr1p and Pdr12p, the mutation leads to reduced cell surface hydrophobicity and decreased virulence of the mutant cells of . The absence of Erg6p impacts the lipid organization and function of the plasma membrane, resulting in non-specific permeability and abrogation of normal function of membrane-bound proteins accompanied by decreased virulence in cells. larvae were used as a non-vertebrate animal host model to determine differences in the virulence potential of strains (parental strain and the deletion mutant). We found that mutant strain attenuated in virulence caused 25-30% survival of larvae compared with parental strain.
该基因编码在麦角固醇生物合成途径中将酵母甾醇转化为粪甾醇的甾醇C24 - 甲基转移酶。在此，我们扩展了该基因功能分析的结果，该基因先前已显示可调节突变细胞中的药物敏感性，通过证明其缺失会导致对环己酰亚胺、4 - 硝基喹啉 - N - 氧化物和弱有机酸的敏感性增加，并且这些效应与毒力减弱相关。与Cdr1p和Pdr12p对药物底物外排的消除一起，该突变导致细胞表面疏水性降低以及该突变细胞的毒力下降。Erg6p的缺失影响质膜的脂质组织和功能，导致非特异性通透性以及膜结合蛋白正常功能的丧失，同时伴随着细胞中毒力的降低。使用幼虫作为非脊椎动物宿主模型来确定菌株（亲本菌株和缺失突变体）毒力潜力的差异。我们发现，与亲本菌株相比，毒力减弱的突变菌株导致幼虫的存活率为25 - 30%。
