Urbanek Aneta K, Łapińska Zofia, Derkacz Daria, Krasowska Anna
Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland.
Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
Pathogens. 2022 Nov 3;11(11):1289. doi: 10.3390/pathogens11111289.
Candidiasis refers to both superficial and deep-tissue fungal infections often caused by . The treatment of choice for these infections is the use of azoles, such as fluconazole (FLC). However, the increased use of antifungal agents has led to the emergence of azole-resistant isolates of . Thus, the development of alternative drugs that are more efficient and with a better toxicological profile is necessary. This study aimed to determine the susceptibility profile of CAF2-1 strain to FLC in the presence of glucose or lactate. The research was also focused on single nucleotide polymorphism (SNP) and the determination of the effect of the identified point mutations on the amino acid sequence of the Erg11 protein. The results show the growth of CAF2-1 in the presence of FLC was significantly lower in the presence of lactate than in glucose. As a result, among recorded 45 amino acid mutations, the following mutations may be associated with the reduced susceptibility of to FLC: G10D, G10V, I11M, I11R, Y13N, F31V, L35F, A249D, Q250H, E266G, R267G, N273K, D275C, D275G, D275R. Moreover, a twice higher number of hot-spot mutations was found in the presence of glucose as a sole carbon source compared to cells grown on lactate.
念珠菌病是指通常由……引起的浅表和深部组织真菌感染。这些感染的首选治疗方法是使用唑类药物，如氟康唑（FLC）。然而，抗真菌药物使用的增加导致了……唑类耐药菌株的出现。因此，开发更高效且毒理学特性更好的替代药物是必要的。本研究旨在确定CAF2-1菌株在葡萄糖或乳酸存在的情况下对FLC的敏感性特征。该研究还聚焦于单核苷酸多态性（SNP）以及所鉴定的点突变对Erg11蛋白氨基酸序列的影响。结果表明，CAF2-1在乳酸存在时，其在FLC存在情况下的生长显著低于在葡萄糖存在时。因此，在记录的45个氨基酸突变中，以下突变可能与……对FLC敏感性降低有关：G10D、G10V、I11M、I11R、Y13N、F31V、L35F、A249D、Q250H、E266G、R267G、N273K、D275C、D275G、D275R。此外，与在乳酸上生长的细胞相比，在仅以葡萄糖作为唯一碳源的情况下发现的热点突变数量高出两倍。
