Effect of progesterone onCandida albicansbiofilm formation under acidic conditions: a transcriptomic analysis

Abstract

23Vulvovaginal candidiasis (VVC) caused by Candida albicans is a common disease 24 worldwide. A very important C. albicans virulence factor is its ability to form biofilms on 25 epithelium and/or on intrauterine devices promoting VVC. It has been shown that VVC has a 26 hormonal dependency and that progesterone affects virulence traits of C. albicans cells. To 27 understand how the acidic environment (pH 4) and progesterone (either alone and in 28 combination) modulate C. albicans response during formation of biofilm, a transcriptomic 29 analysis was performed together with characterization of the biofilm properties. Compared to 30 planktonic cells, acidic biofilm-cells exhibited major changes in their transcriptome, including 31 modifications in the expression of 286 genes that were not previously associated with biofilm 32 formation in C. albicans. The vast majority of the genes up-regulated in the acidic biofilm cells 33 (including those uniquely identified here) are known targets of Sfl1, and the expression of this 34 regulator impaired formation of the acidic biofilm. Under the acidic conditions used, 35 progesterone treatment reduced C. albicans biofilm biomass, structural cohesion, matrix 36 quantity and susceptibility to fluconazole. Transcriptomic analysis of progesterone-exposed 37 biofilms led to the identification of 65 down-regulated genes including, among others, the 38 regulator Tec1 and several of its target genes suggesting that the function of this transcription 39 factor is inhibited by the presence of the hormone. Overall, the results of this study show that 40 progesterone modulates C. albicans biofilm formation and genomic expression under acidic 41 conditions, which may have implications for C. albicans pathogenicity in the vaginal 42 environment. 43 44 49 to vaginal microflora, however under certain conditions they can cause infection. It has been 50 shown that conditions that prompt VVC include those leading to high progesterone levels, as 51 pregnancy. Here we show that progesterone impairs the ability of C. albicans cells to form 52 biofilms but causes a potential protective stress response. Indeed, we reveal an increased 53 fluconazole resistance of biofilm cells grown in the presence of the hormone. Additionally, our 54 results suggest that biofilm cells have a specific response to acidic conditions, as those 55 established in the vaginal environment. Deepening the knowledge on the modulation of C. 56 albicans virulence by vaginal conditions is essential for a full understanding of the 57 pathogenesis of this species in the vaginal tract and contribute to the disclosure of new targets 58 to treat VVC. 59 60 65 Infections of this niche therefore have the potential to result in a severe disseminated infection, 66 particularly in immunocompromised patients [2]. Candida species are opportunistic microbes 67 of the commensal microflora, which under certain conditions can transform from symptomless 68 colonization into infection. Most (if not all) women carry Candida cells in the vaginal tr...