耳念珠菌通常与生物膜相关的侵袭性感染有关。这些生物膜的抗性特征需要创新的治疗选择,其中,群体感应可能是潜在的目标。法尼醇和酪醇是两种真菌群体感应分子,在超生理浓度下具有抗真菌作用。这里,我们使用转录组测序(RNA-Seq)在法尼醇或酪醇暴露后,对金丝酵母生物膜进行了全基因组转录谱分析.由于过渡金属在真菌毒力和生物膜形成中起着核心作用,细胞内钙的水平,镁,和铁在法尼醇或酪醇处理后使用电感耦合等离子体发射光谱法测定。法尼醇导致钙和镁含量显着降低89.9%和73.8%,分别,而酪醇导致82.6%,76.6%,钙减少81.2%,镁,和铁含量,分别,与对照相比。参与生物膜事件的基因,糖酵解,麦角甾醇生物合成,脂肪酸氧化,铁代谢,自噬主要在处理的细胞中受到影响。为了证明麦角甾醇群体感应分子相互作用,进行了基于微量稀释的敏感性测试,法尼醇的络合,但不是酪醇,在外源麦角甾醇的存在下,麦角甾醇受到阻碍,导致群体感应分子的最小抑制浓度增加。这项研究揭示了几种法尼醇和酪醇特异性反应,这将有助于开发针对C.auris生物膜的替代疗法。
目的:耳念珠菌是一种多药耐药的真菌病原菌,这通常与生物膜相关的感染有关。念珠菌来源的群体感应分子(法尼醇和酪醇)在真菌形态发生和生物膜发育的调节中起关键作用。此外,它们可能具有显著的抗生物膜作用,尤其是在超生理浓度下。干扰群体感应的创新治疗方法可能是针对C.auris生物膜的有前途的未来策略;然而,目前关于法尼醇诱导的和酪醇相关的分子效应的数据有限。这里,我们检测到几个与生物膜事件有关的基因,糖酵解,麦角甾醇生物合成,脂肪酸氧化,铁代谢,和自噬,主要受法尼醇或酪醇暴露后的影响。此外,钙,镁,铁稳态也受到显著影响。这些结果揭示了这些分子和生理事件,这可能支持针对C.auris生物膜的新型治疗方法的开发。
Candida auris is frequently associated with biofilm-related invasive infections. The resistant profile of these biofilms necessitates innovative therapeutic options, where quorum sensing may be a potential target. Farnesol and tyrosol are two fungal quorum-sensing molecules with antifungal effects at supraphysiological concentrations. Here, we performed genome-wide transcript profiling with C. auris biofilms following farnesol or tyrosol exposure using transcriptome sequencing (RNA-Seq). Since transition metals play a central role in fungal virulence and biofilm formation, levels of intracellular calcium, magnesium, and iron were determined following farnesol or tyrosol treatment using inductively coupled plasma optical emission spectrometry. Farnesol caused an 89.9% and 73.8% significant reduction in the calcium and magnesium content, respectively, whereas tyrosol resulted in 82.6%, 76.6%, and 81.2% decrease in the calcium, magnesium, and iron content, respectively, compared to the control. Genes involved in biofilm events, glycolysis, ergosterol biosynthesis, fatty acid oxidation, iron metabolism, and autophagy were primarily affected in treated cells. To prove ergosterol quorum-sensing molecule interactions, microdilution-based susceptibility testing was performed, where the complexation of farnesol, but not tyrosol, with ergosterol was impeded in the presence of exogenous ergosterol, resulting in a minimum inhibitory concentration increase in the quorum-sensing molecules. This study revealed several farnesol- and tyrosol-specific responses, which will contribute to the development of alternative therapies against C. auris biofilms.
OBJECTIVE: Candida auris is a multidrug-resistant fungal pathogen, which is frequently associated with biofilm-related infections. Candida-derived quorum-sensing molecules (farnesol and tyrosol) play a pivotal role in the regulation of fungal morphogenesis and biofilm development. Furthermore, they may have remarkable anti-biofilm effects, especially at supraphysiological concentrations. Innovative therapeutic approaches interfering with quorum sensing may be a promising future strategy against C. auris biofilms; however, limited data are currently available concerning farnesol-induced and tyrosol-related molecular effects in C. auris. Here, we detected several genes involved in biofilm events, glycolysis, ergosterol biosynthesis, fatty acid oxidation, iron metabolism, and autophagy, which were primarily influenced following farnesol or tyrosol exposure. Moreover, calcium, magnesium, and iron homeostasis were also significantly affected. These results reveal those molecular and physiological events, which may support the development of novel therapeutic approaches against C. auris biofilms.