Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, MB, Canada.
Department of Statistics, Faculty of Science, University of Manitoba, Winnipeg, MB, Canada.
Can J Microbiol. 2024 Sep 1;70(9):384-393. doi: 10.1139/cjm-2023-0225. Epub 2024 Jul 31.
Boric acid is a broad-spectrum antimicrobial used to treat vulvovaginal candidiasis when patients relapse on the primary azole drug fluconazole. is the most common cause of vulvovaginal candidiasis, colloquially referred to as a "vaginal yeast infection". Little is known about the propensity of to develop BA resistance or tolerance (the ability of a subpopulation to grow slowly in high levels of drug). We evolved 96 replicates from eight diverse strains to increasing BA concentrations to test the evolvability of BA resistance and tolerance. Replicate growth was individually assessed daily, with replicates passaged when they had reached an optical density consistent with exponential growth. Many replicates went extinct quickly. Although some replicates could grow in much higher levels of BA than the ancestral strains, evolved populations isolated from the highest terminal BA levels (after 11 weeks of passages) surprisingly showed only modest growth improvements and only at low levels of BA. No large increases in resistance or tolerance were observed in the evolved replicates. Overall, our findings illustrate that there may be evolutionary constraints limiting the emergence of BA resistance and tolerance, which could explain why it remains an effective treatment for recurrent yeast infections.
硼酸是一种广谱抗菌药物，用于治疗在使用唑类药物氟康唑治疗原发性疾病后复发的外阴阴道念珠菌病。白色念珠菌是外阴阴道念珠菌病的最常见原因，俗称“阴道酵母菌感染”。关于白色念珠菌产生硼酸耐药性或耐受性（亚群在高浓度药物中缓慢生长的能力）的倾向知之甚少。我们从 8 株不同的白色念珠菌进化了 96 个复制品，以增加硼酸浓度，以测试硼酸耐药性和耐受性的可进化性。每天单独评估复制体的生长情况，当复制体达到与指数生长一致的光密度时，将其传代。许多复制品很快就灭绝了。尽管一些复制体可以在比原始菌株高得多的硼酸水平下生长，但从最高终端硼酸水平（经过 11 周的传代）分离出来的进化种群的生长改善却令人惊讶地仅适度提高，而且仅在低水平的硼酸下。在进化复制体中未观察到耐药性或耐受性的大幅增加。总的来说，我们的研究结果表明，可能存在进化限制，限制了硼酸耐药性和耐受性的出现，这可以解释为什么硼酸仍然是治疗复发性酵母菌感染的有效药物。
