Constraint on boric acid resistance and tolerance evolvability inCandida albicans

Abstract

Boric acid is a broad-spectrum antimicrobial used to treat vulvovaginal candidiasis when patients relapse on the primary azole drug fluconazole. Candida albicans is the most common cause of vulvovaginal candidiasis, colloquially referred to as a "vaginal yeast infection". Little is known about the propensity of C. albicans 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 genotypically diverse C. albicans strains to increasing BA concentrations to examine whether they would evolve BA resistance and/or tolerance. We found that many replicates went extinct quickly. Although some replicates were able to grow in much higher levels of BA than the ancestral strains, evolved populations isolated from the highest terminal BA levels 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.