Gupta Payal, Gupta Hrishikesh, Kairamkonda Manikyaprabhu, Kumar Navin, Poluri Krishna Mohan
Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee-247667, Uttarakhand, India.
Department of Biotechnology, Graphic Era University, Dehradun-248001, Uttarakhand, India.
Med Mycol. 2022 Jun 9. doi: 10.1093/mmy/myac042.
Incidence of vulvovaginal candidiasis are strikingly high and treatment options are limited with nearly 50% Candida glabrata cases left untreated or experience treatment failures. The vaginal microenvironment is rich in lactic acid, and the adaptation of C. glabrata to lactic acid (LA) is the main reason for clinical treatment failure. In the present study, C. glabrata and its vaginal clinical isolates were comprehensively investigated for their growth response, metabolic adaptation and altered cellular pathway to LA using different biochemical techniques, metabolic profiling and transcriptional studies. C. glabrata shown considerable variations in its topological and biochemical features without compromising growth in LA media. Chemical profiling data highlighted involvement of cell wall/membrane, ergosterol and oxidative stress related pathways in mediating adaptative response of C. glabrata towards LA. Further, one dimensional proton (1H) NMR spectroscopy based metabolic profiling revealed significant modulation in 19 metabolites of C. glabrata cells upon growth in LA. Interestingly myo-inositol, xylose, putrescine and betaine which are key metabolites for cell growth and viability were found to be differentially expressed by clinical isolates. These observations were supported by the transcriptional expression study of selected genes evidencing cell wall/membrane re-organisation, altered oxidative stress, and reprogramming of carbon metabolic pathways. Collectively, the study advances our understanding on adaptative response of C. glabrata in vaginal microenvironment to lactic acid for survival and virulence.
外阴阴道念珠菌病的发病率极高，治疗选择有限，近50%的光滑念珠菌病例未得到治疗或治疗失败。阴道微环境富含乳酸，光滑念珠菌对乳酸（LA）的适应性是临床治疗失败的主要原因。在本研究中，使用不同的生化技术、代谢谱分析和转录研究，对光滑念珠菌及其阴道临床分离株在生长反应、代谢适应性和细胞途径对LA的改变方面进行了全面研究。光滑念珠菌在拓扑和生化特征上表现出相当大的差异，但不影响其在LA培养基中的生长。化学谱分析数据突出了细胞壁/膜、麦角固醇和氧化应激相关途径在介导光滑念珠菌对LA的适应性反应中的作用。此外，基于一维质子（1H）核磁共振光谱的代谢谱分析显示，光滑念珠菌细胞在LA中生长后，19种代谢物有显著调节。有趣的是，临床分离株发现，作为细胞生长和活力关键代谢物的肌醇、木糖、腐胺和甜菜碱表达存在差异。这些观察结果得到了所选基因转录表达研究的支持，该研究证明了细胞壁/膜的重新组织、氧化应激的改变以及碳代谢途径的重新编程。总体而言，该研究推进了我们对光滑念珠菌在阴道微环境中对乳酸的适应性反应以实现生存和毒力的理解。
