Antifungal mechanisms supporting boric acid therapy of Candida vaginitis
Antifungal mechanisms supporting boric acid therapy of Candida vaginitis
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DOI：
10.1093/jac/dkn486
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发表时间：
2009-02-01
影响因子：
5.2
通讯作者：
Larsen, Bryan
中科院分区：
文献类型：
--
作者：
De Seta, Francesco;Schmidt, Martin;Larsen, Bryan
硼酸是一种常用的治疗复发和耐药的酵母菌阴道炎的方法，但关于其抗真菌活性的程度和机制的数据尚不多见。本研究的目的是利用体外方法了解硼酸作为一种潜在的治疗阴道感染的方法的光谱和机制。已建立的微生物生理学方法阐明了硼酸对白色念珠菌的作用机制。白色念珠菌株(包括氟康唑耐药株)在阴道内可获得的浓度下被抑制；细菌也是如此。肉汤稀释度MIC在1563至6250 mg/L之间，硼酸证明有抑菌作用(二氧化碳产生量的减少也反映了这一点)；长期培养在50000 mg/L有杀菌作用。酵母氮气发酵液中的几种有机酸的pH值低于等摩尔硼酸和硼酸钠，但抑制作用较小。低温或厌氧培养可保护酵母在高浓度的硼酸环境中生长。细胞在37℃的硼酸中保持6小时的完整性，但在24小时后出现适度的碘化丙啶侵入；在摄取生命染色之前，平板计数活力丧失。在亚MIC浓度下生长的硼酸降低了细胞麦角甾醇。药物外排泵CDR1不能保护念珠菌，因为CDR1的表达被硼酸抑制。硼酸干扰了生物膜的形成和菌丝转化，对杀菌剂的抑菌作用依赖于浓度和温度。抑制氧化代谢似乎是一个关键的抗真菌机制，但抑制毒力可能有助于体内的治疗效果。
Boric acid is a commonly cited treatment for recurrent and resistant yeast vaginitis, but data about the extent and mechanism of its antifungal activity are lacking.The aim of this study was to use in vitro methods to understand the spectrum and mechanism of boric acid as a potential treatment for vaginal infection.Yeast and bacterial isolates were tested by agar dilution to determine the intrinsic antimicrobial activity of boric acid. Established microbial physiology methods illuminated the mechanism of the action of boric acid against Candida albicans.C. albicans strains (including fluconazole-resistant strains) were inhibited at concentrations attainable intravaginally; as were bacteria. Broth dilution MICs were between 1563 and 6250 mg/L and boric acid proved fungistatic (also reflected by a decrease in CO2 generation); prolonged culture at 50 000 mg/L was fungicidal. Several organic acids in yeast nitrogen broth yielded a lower pH than equimolar boric acid and sodium borate but were less inhibitory. Cold or anaerobic incubation protected yeast at high boric acid concentrations. Cells maintained integrity for 6 h in boric acid at 37 degrees C, but after 24 h modest intrusion of propidium iodide occurred; loss of plate count viability preceded uptake of vital stain. Growth at sub-MIC concentrations of boric acid decreased cellular ergosterol. The drug efflux pump CDR1 did not protect Candida as CDR1 expression was abrogated by boric acid. Boric acid interfered with the development of biofilm and hyphal transformation.Boric acid is fungistatic to fungicidal depending on concentration and temperature. Inhibition of oxidative metabolism appears to be a key antifungal mechanism, but inhibition of virulence probably contributes to therapeutic efficacy in vivo.