Anti-Biofilm Activity of Phenyllactic Acid against Clinical Isolates of Fluconazole-Resistant Candida albicans

Abstract

Commonly found colonizing the human microbiota, <i>Candida albicans</i> is a microorganism known for its ability to cause infections, mainly in the vulvovaginal region, and is responsible for 85% to 90% of vulvovaginal candidiasis (VVC) cases. The development of drug resistance in <i>C. albicans</i> isolates after long-term therapy with fluconazole is an important complication to solve and new therapeutic strategies are required to target this organism and its pathogenicity. In the present study, phenyllactic acid (PLA) an important broad-spectrum antimicrobial compound was investigated for its antifungal and antivirulence activities against clinical isolates of <i>C. albicans</i>. Previously characterized strains of <i>C. albicans</i> isolates from women with VVC and <i>C. albicans</i> ATCC90028 were used to evaluate the antimicrobial and time dependent killing assay activity of PLA showing a MIC 7.5 mg mL^-1 and a complete reduction of viable <i>Candida</i> cells detected by killing kinetics after 4 h of treatment with PLA. Additionally, PLA significantly reduced the biomass and the metabolic activity of <i>C. albicans</i> biofilms and impaired biofilm formation also with changes in <i>ERG11</i>, <i>ALS3</i>, and <i>HWP1</i> genes expression as detected by qPCR. PLA eradicated pre-formed biofilms as showed also with confocal laser scanning microscopy (CLSM) observations. Furthermore, the compound prolonged the survival rate of <i>Galleria mellonella</i> infected by <i>C. albicans</i> isolates. These results indicate that PLA is a promising candidate as novel and safe antifungal agents for the treatment of vulvovaginal candidiasis.