1 Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Bratislava, Slovakia.
2 Faculty of Mathematics and Physics, Institute of Physics, Charles University, Prague, Czech Republic.
Microb Drug Resist. 2019 Jul/Aug;25(6):805-812. doi: 10.1089/mdr.2017.0332. Epub 2019 Feb 20.
This work studied the impact of the quorum-sensing molecule, farnesol (FAR), on fluconazole (FLC)-resistant isolate CY 1123 compared with the susceptible standard strain SC5314. The genes encoding efflux pumps belonging to the ATP-binding cassette (ABC) and major facilitator superfamilies, together with overexpression or point mutation of the gene, are the main resistance mechanisms to azole antifungal drugs. The upregulation of genes coding for and were confirmed by qPCR with respect to the housekeeping gene in the resistant strain. The contribution of the gene was also observed. Markedly, increased pump activity (Cdr1 and/or Cdr2) in the CY 1123 strain was confirmed using diS-C(3) assay. However, the addition of FAR to the yeasts diminished the difference in staining levels between the SC5314 and CY 1123 strains, demonstrating the concentration-dependent character that could be caused by an effective modulation of Cdr pumps. FAR (60 and 100 μM) was also able to decrease the minimal inhibitory concentrations (MIC), denoting the inhibition of planktonic cells by 50%, from 8 to 4 μg/mL of FLC when the resistant strain CY 1123 was not cultivated with FLC. However, when it was exposed to 64 μg/mL of FLC, the MIC shifted from 64 to 8 μg/mL. Besides the many other effects of FAR on eukaryotic and prokaryotic cells, it also affects ABC efflux transporters, resulting in changes in resistance to azoles in isolates. However, this effect is dependent on FAR concentrations.
这项工作研究了群体感应分子法呢醇（FAR）对氟康唑（FLC）耐药分离株 CY 1123 的影响，与敏感标准株 SC5314 相比。编码属于三磷酸腺苷结合盒（ABC）和主要易化子超家族的外排泵的基因，以及基因的过表达或点突变，是对唑类抗真菌药物产生耐药性的主要机制。通过 qPCR 相对于管家基因，对耐药菌株中编码和的基因进行了上调。还观察到基因的贡献。值得注意的是，在 CY 1123 菌株中，使用 diS-C(3) 测定法证实了泵活性（Cdr1 和/或 Cdr2）的增加。然而，将 FAR 添加到酵母中，降低了 SC5314 和 CY 1123 菌株之间染色水平的差异，表明存在浓度依赖性特征，这可能是由于 Cdr 泵的有效调节所致。FAR（60 和 100 μM）还能够降低最小抑菌浓度（MIC），表示当耐药菌株 CY 1123 未与 FLC 一起培养时，从 8 至 4 μg/mL 的 FLC 抑制浮游细胞的 50%。然而，当它暴露于 64 μg/mL 的 FLC 时，MIC 从 64 变为 8 μg/mL。除了 FAR 对真核和原核细胞的许多其他影响外，它还影响 ABC 外排转运蛋白，导致唑类在分离株中的耐药性发生变化。然而，这种效应取决于 FAR 浓度。
