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Transcriptome Analyses of Candida albicans Biofilms, Exposed to Arachidonic Acid and Fluconazole, Indicates Potential Drug Targets.
G3: Genes, Genomes, Genetics ( IF 2.1 ) Pub Date : 2020-09-01 , DOI: 10.1534/g3.120.401340
Oluwasegun Kuloyo 1 , Ruan Fourie 1 , Errol Cason 1 , Jacobus Albertyn 1 , Carolina H Pohl 2
Affiliation  

Candida albicans 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 C. albicans 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. Protein ANalysis THrough Evolutionary Relationships (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.



中文翻译:

暴露于花生四烯酸和氟康唑的白色念珠菌生物膜的转录组分析表明潜在的药物靶标。

白色念珠菌是人微生物区系中的机会酵母病原体,由于其致病潜力而具有重要的医学重要性。酵母产生高抗性的生物膜,这对于维持感染至关重要。尽管可以使用抗真菌药,但由于抗药性,其有效性正在下降。已显示出将现有唑与多不饱和脂肪酸(如花生四烯酸(AA))结合使用的替代方法会增加白色念珠菌对唑的敏感性生物膜 但是,机制仍然未知。因此,对暴露于亚抑制浓度的AA,单独的氟康唑和AA与氟康唑的亚抑制浓度的生物膜进行转录组分析,以了解与该现象有关的可能机制。P蛋白质 一个分析 THË进化的 [R差异表达基因的相关性(PANTHER)分析显示,AA和氟康唑的组合会影响与必需过程相关的生物过程,这些过程包括蛋氨酸合成以及涉及ATP生成的那些过程,例如AMP生物合成,富马酸酯代谢和脂肪酸氧化。这些观察结果表明,AA对这些过程的干扰可能是诱导增加的抗真菌药性的可能机制。

更新日期:2020-09-02
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