Hormones modulate Candida vaginal isolates biofilm formation and decrease their susceptibility to azoles and hydrogen peroxide

Abstract

Vulvovaginal candidiasis (VVC) is an infection usually caused by Candida albicans and increasingly by Candida glabrata, which has an intrinsically high resistance to commonly used antifungals. Candida species possess virulence factors that contribute to VVC development, as the ability to form biofilms in vaginal walls and intrauterine devices. It is known that VVC is promoted by conditions that increase the hormones levels, during pregnancy, however, the effects of hormones on Candida cells are poorly studied, especially in C. glabrata. Thus, the influence of progesterone and β-estradiol, at normal cycle and pregnancy concentrations, on biofilm formation and resistance of C. albicans and C. glabrata vaginal isolates, was analyzed using acidic conditions (pH 4). Biofilms of C. albicans developed in the presence of hormones presented reduced biomass (up to 65%) and impaired cells ability to produce filamentous forms. On the other hand, C. glabrata presented high adaptation to the presence of hormones, which did not affect its biofilm formation. Additionally, hormones impaired the susceptibility of C. albicans and C. glabrata cells to azoles, with potential clinical significance in the presence of pregnancy hormone levels. A similar result was obtained for the susceptibility to hydrogen peroxide, a biological vaginal barrier against Candida growth. Overall, the results of this study suggest that hormones may act as environmental cues promoting Candida protection from vaginal defenses and harmful conditions, what may have implications in Candida vaginal pathogenicity and treatment of VVC, especially in C. glabrata infections due to its high adaptability to vaginal conditions.

Candida glabrata Antifungal Resistance and Virulence Factors, a Perfect Pathogenic Combination

“…The findings coincide with a study conducted by Gonçalves et al, where they analyzed the effect of progesterone and β-estradiol on the production of biofilms in C. glabrata and C. albicans . They noted that hormones do not influence the generation of biofilms in C. glabrata , but they reduce biofilm formation in C. albicans by more than 65% [ 205 ].…”

“…Finally, they suggest that hormones act as environmental signals that promote the protection of Candida spp. [ 205 ]. This is related to what Beyer et al described when they observed that CgHog1, a high-osmolarity glycerol response MAP kinase that contributes to C. glabrata persistence inside mice macrophages, may be the main quantitative determinant of lactic acid stress resistance.…”

Candidiasis vulvovaginal recurrente

“…La formación de biofilm es un mecanismo altamente reconocido en especies de cándida, principalmente en C. albicans y se ha visto que la formación de este biolfilm es de los principales mecanismo de resistencia y falla terapéutica a los antifúngicos ante los casos de candidiasis vaginal pero no así de la candidiasis vaginal recurrente en donde se ha visto que el tipo de especie predominante y los mecanismos de resistencia son distintos al de la candidiasis vaginal simple, sin embargo, es un campo que aún debe ser estudiado para lograr entender la poca respuesta a los antifúngicos en la candidiasis vaginal recurrente (10). Gonçalves et al realizaron un estudio con cepas de C. albicans y C. glabatra en donde el efecto de las hormonas reproductivas sobre la proliferación de las especies de cándida y la capacidad de estas hormonas de modular los mecanismos de defensa del microorganismo así como la cantidad de cepas altamente virulentas que se puedan reproducir, se logró observar que la susceptibilidad reducida a los azoles así como el estrés oxidativo sugiere que las hormonas reproductivas pueden promover la sobrevivencia de las especies de cándida así como su adaptación al medio vaginal, se vio además, que la especie de C. glabratra la cual además fue aislada en varias de las infecciones recurrentes, tiene una mayor adaptación al estrés hormonal y capacidad de formación de biofilm ante las condiciones del medio vaginal, no así las cepas de C. albicans que si presentaron una disminución en capacidad de formación de biofilm ante los efectos de las hormonas reproductivas a nivel vaginal (11). Múltiples estudios de cohorte han demostrado una alta susceptibilidad de candidiasis vulvovaginal recurrente en mujeres que presentan diversos polimorfismos genéticos, así como asociado a diversas etnias y fallos en la respuesta inmunológica, sin embargo, es un campo que aún debe ser estudiado con profundidad (12).…”

Identification of female genital tract infectious agents in patients treated for cytopathological diagnosis

“…e de uma intervenção terapêutica adequada, dado ao número relevante da presença de espécies não-albicans. Isto porque, mesmo não sendo considerada uma doença sexualmente transmissível, a candidíase vulvovaginal ocorre em um grande número de mulheres, afetando sua qualidade de vida e gerando desconfortos imensuráveis (Tozzo, Grazziotin, 2012;Gonçalves et al, 2019).…”