Department of Microbial, Biochemical, and Food Biotechnology, University of the Free State, Bloemfontein, South Africa 9301.
Department of Microbial, Biochemical, and Food Biotechnology, University of the Free State, Bloemfontein, South Africa 9301
G3 (Bethesda). 2020 Sep 2;10(9):3099-3108. doi: 10.1534/g3.120.401340.
is an opportunistic yeast pathogen within the human microbiota with significant medical importance because of its pathogenic potential. The yeast produces highly resistant biofilms, which are crucial for maintaining infections. Though antifungals are available, their effectiveness is dwindling due to resistance. Alternate options that comprise the combination of existing azoles and polyunsaturated fatty acids, such as arachidonic acid (AA), have been shown to increase azoles susceptibility of biofilms; however, the mechanisms are still unknown. Therefore, transcriptome analysis was conducted on biofilms exposed to sub-inhibitory concentrations of AA alone, fluconazole alone, and AA combined with fluconazole to understand the possible mechanism involved with the phenomenon. rotein alysis rough volutionary elationships (PANTHER) analysis from the differentially expressed genes revealed that the combination of AA and fluconazole influences biological processes associated with essential processes including methionine synthesis and those involved in ATP generation, such as AMP biosynthesis, fumarate metabolism and fatty acid oxidation. These observations suggests that the interference of AA with these processes may be a possible mechanisms to induce increased antifungal susceptibility.
是一种机会性酵母病原体,存在于人类微生物群中,由于其潜在的致病性,具有重要的医学意义。该酵母产生高度耐药的生物膜,这对于维持感染至关重要。尽管有抗真菌药物可用,但由于耐药性,其效果正在减弱。已经表明,包含现有唑类药物和多不饱和脂肪酸(如花生四烯酸(AA))组合的替代方案可以增加生物膜中唑类药物的敏感性;然而,其机制仍不清楚。因此,对暴露于亚抑制浓度的 AA 单独、氟康唑单独以及 AA 与氟康唑联合的生物膜进行了转录组分析,以了解可能涉及这一现象的可能机制。从差异表达基因中进行的蛋白质rough 进化关系(PANTHER)分析表明,AA 和氟康唑的联合影响与基本过程相关的生物学过程,包括蛋氨酸合成和与 ATP 生成相关的过程,如 AMP 生物合成、富马酸代谢和脂肪酸氧化。这些观察结果表明,AA 对这些过程的干扰可能是诱导增加抗真菌敏感性的一种可能机制。