Vulvovaginal candidiasis (VVC) caused by Candida albicans is a common disease worldwide. A very important C. albicans virulence factor is its ability to form biofilms on epithelium and/or on intrauterine devices promoting VVC. It has been shown that VVC has a hormonal dependency and that progesterone affects virulence traits of C. albicans cells. To understand how the acidic environment (pH 4) and progesterone (either alone and in combination) modulate C. albicans response during formation of biofilm, a transcriptomic analysis was performed together with characterization of the biofilm properties. Compared to planktonic cells, acidic biofilm-cells exhibited major changes in their transcriptome, including modifications in the expression of 286 genes that were not previously associated with biofilm formation in C. albicans. The vast majority of the genes up-regulated in the acidic biofilm cells (including those uniquely identified in our study) are known targets of Sfl1, and consistently, Sfl1 deletion is herein shown to impair the formation of acidic biofilms (pH 4). Under the acidic conditions used, the presence of progesterone reduced C. albicans biofilm biomass and structural cohesion. Transcriptomic analysis of biofilms developed in the presence of progesterone led to the identification of 65 down-regulated genes including, among others, the regulator Tec1 and several of its target genes, suggesting that the function of this transcription factor is inhibited by the presence of the hormone. Additionally, progesterone reduced the susceptibility of biofilm cells to fluconazole, consistent with an up-regulation of efflux pumps. Overall, the results of this study show that progesterone modulates C. albicans biofilm formation and genomic expression under acidic conditions, which may have implications for C. albicans pathogenicity in the vaginal environment.

由白色念珠菌引起的外阴念珠菌病（VVC）是世界范围内的常见疾病。一个非常重要的白色念珠菌毒力因子是其在上皮和/或在宫腔内促进VVC的装置上形成生物膜的能力。已经表明，VVC具有激素依赖性，并且孕酮影响白色念珠菌细胞的毒力特性。了解酸性环境（pH 4）和孕酮（单独或联合使用）如何调节白色念珠菌生物膜形成过程中的应答，进行了转录组分析以及生物膜特性的表征。与浮游细胞相比，酸性生物膜细胞在转录组上表现出重大变化，包括以前与白念珠菌生物膜形成无关的286个基因表达的修饰。酸性生物膜细胞中上调的绝大多数基因（包括我们研究中唯一鉴定的那些基因）是Sfl1的已知靶标，并且一致地，本文显示Sfl1缺失会削弱酸性生物膜的形成（pH 4）。在酸性条件下，孕酮的存在会降低白色念珠菌生物膜生物量和结构内聚力。在孕酮存在下形成的生物膜的转录组学分析导致​​鉴定了65个下调基因，其中包括调节子Tec1及其几个靶基因，这表明该转录因子的功能受到存在的抑制。激素。此外，孕激素降低了生物膜细胞对氟康唑的敏感性，这与外排泵的上调一致。总体而言，这项研究的结果表明，孕酮在酸性条件下调节白色念珠菌生物膜的形成和基因组表达，这可能对阴道环境中的白色念珠菌致病性有影响。