Successful colonization of the acidic vaginal niche by C. glabrata and C. albicans depends on their ability to cope with the presence of lactic and acetic acids produced by commensal microbiota. As such, the inhibitory effect of these acids at a low pH in growth of C. glabrata and C. albicans was investigated. The effect of the presence of these organic acids in tolerance of the two Candida species to azoles used in treatment of vaginal infections was also investigated including eventual synergistic effects. Under the different experimental conditions tested lactic acid exerted no significant inhibitory effect against C. albicans or C. glabrata, contrasting with the generalized impression that the production of this acid is on the basis of the protective effect exerted by vaginal lactobacilii. Differently, C. glabrata and C. albicans exhibited susceptibility to acetic acid, more prominent at lower pHs and stronger for the latter species. Synergism between acetic acid and azoles was observed both for C. albicans and C. glabrata, while lactic acid-azole synergism was only efficient against C. albicans. Altogether our in vitro results indicate that tolerance to acetic acid at a low pH may play a more relevant role than tolerance to lactic acid in determining competitiveness in the vaginal tract of C. albicans and C. glabrata including under azole stress. Treatment of vaginal candidiasis with azoles may depend on the level of acetic and lactic acids present and improvements could be achieved synergizing the azole with these acids.

Fungal infections and, in particular, those caused by species of the Candida genus, are growing at an alarming rate and have high associated rates of mortality and morbidity. These infections, generally referred as candidiasis, range from common superficial rushes caused by an overgrowth of the yeasts in mucosal surfaces to life-threatening disseminated mycoses. The success of currently used antifungal drugs to treat candidiasis is being endangered by the continuous emergence of resistant strains, specially among non-albicans Candida species. In this review article, the mechanisms of action of currently used antifungals, with emphasis on the mechanisms of resistance reported in clinical isolates, are reviewed. Novel approaches being taken to successfully inhibit growth of pathogenic Candida species, in particular those based on the exploration of natural or synthetic chemicals or on the activity of live probiotics, are also reviewed. It is expected that these novel approaches, either used alone or in combination with traditional antifungals, may contribute to foster the identification of novel anti-Candida therapies.

Zinc (Zn)-derived foams have been prepared from an alkaline electrolyte solution by galvanostatic electrodeposition under different conditions. The resulting 316L stainless steel (SS) coated with two distinct Zn-derived foams was tested in the inhibition of osteoscarcoma cell proliferation and C. albicans colonization.

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The exploration of the interference prompted by commensal bacteria over fungal pathogens is an interesting alternative to develop new therapies. In this work we scrutinized how the presence of the poorly studied vaginal species Lactobacillus gasseri affects relevant pathophysiological traits of Candida albicans and Candida glabrata. L. gasseri was found to form mixed biofilms with C. albicans and C. glabrata resulting in pronounced death of the yeast cells, while bacterial viability was not affected. Reduced viability of the two yeasts was also observed upon co-cultivation with L. gasseri under planktonic conditions. Either in planktonic cultures or in biofilms, the anti-Candida effect of L. gasseri was augmented by acetate in a concentration-dependent manner. During planktonic co-cultivation the two Candida species counteracted the acidification prompted by L. gasseri thus impacting the balance between dissociated and undissociated organic acids. This feature couldn’t be phenocopied in single-cultures of L. gasseri resulting in a broth enriched in acetic acid, while in the co-culture the non-toxic acetate prevailed. Altogether the results herein described advance the design of new anti-Candida therapies based on probiotics, in particular, those based on vaginal lactobacilli species, helping to reduce the significant burden that infections caused by Candida have today in human health.

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...