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激素调节阴道念珠菌分离物生物膜的形成,并降低其对唑类药物和过氧化氢的敏感性。

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

机构信息

CEB, Center of Biological Engineering, LIBRO - "Laboratório de Investigação em Biofilmes Rosário Oliveira", University of Minho, Gualtar Campus, 4715-057 Braga, Portugal.

出版信息

Med Mycol. 2020 Apr 1;58(3):341-350. doi: 10.1093/mmy/myz070.

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.

摘要

外阴阴道念珠菌病(VVC)通常由白念珠菌引起,并且越来越多的由对常用抗真菌药物具有固有高抗性的近平滑念珠菌引起。念珠菌属具有有助于 VVC 发展的毒力因子,因为其具有在阴道壁和宫内装置中形成生物膜的能力。已知 VVC 是由增加激素水平的情况促进的,例如在怀孕期间,然而,激素对念珠菌细胞的影响尚未得到充分研究,尤其是在近平滑念珠菌中。因此,分析了孕激素和β-雌二醇在正常周期和妊娠浓度下对白色念珠菌和近平滑念珠菌阴道分离株生物膜形成和耐药性的影响,使用酸性条件(pH4)。在激素存在下形成的白色念珠菌生物膜表现出减少的生物量(高达 65%)和受损的细胞产生丝状形态的能力。另一方面,近平滑念珠菌对激素的存在具有高度适应性,这不会影响其生物膜形成。此外,激素降低了白色念珠菌和近平滑念珠菌细胞对唑类药物的敏感性,这在妊娠激素水平存在时具有潜在的临床意义。对过氧化氢的敏感性也得到了类似的结果,过氧化氢是一种生物性阴道屏障,可抵抗念珠菌生长。总的来说,这项研究的结果表明,激素可能作为环境线索,促进念珠菌免受阴道防御和有害条件的侵害,这可能对念珠菌阴道致病性和 VVC 的治疗产生影响,尤其是在由于其对阴道条件的高适应性而导致的近平滑念珠菌感染时。

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