Anti-fungal efficacy of Carvacrol against Candida glabrata clinical isolates of vulvovaginal candidiasis

Fungal infections affect over 1 billion people worldwide each year, including superficial infections like athlete's foot and more severe systemic infections. Fungal diseases are responsible for an estimated 1.5 million deaths annually, a figure comparable to or exceeding the mortality rate of diseases like malaria or tuberculosis. The limited arsenal of available antifungal drugs, coupled with the emergence of drug-resistant fungal strains, has increased this concern. Therefore, there is a significant need to explore alternative therapeutics to overcome fungal pathogens. Carvacrol, phenolic monoterpenoids, is present in essential oils of many plants and is known for its biological and pharmacological properties. In the present study, the efficacy of carvacrol was investigated against four Candida glabrata strains isolated from patients of vulvovaginal candidiasis, which have shown varying extents of susceptibility against fluconazole. Carvacrol, a phytoactive monoterpene phenol, has shown a minimum inhibitory concentration (MIC50) ranging from 75 to 125 µg/mL and minimum fungicidal concentration of 150 and 175 µg/mL for all clinical isolates, including wild-type strains. Carvacrol, in combination with fluconazole, has shown a strong synergism against wild type C. glabrata with a FIC index value of 0.156. Preliminary mechanistic investigations unveiled that exposure to carvacrol significantly reduced cell surface hydrophobicity and ergosterol content in all strains. In conclusion, carvacrol holds promising potential as an effective antifungal agent against C. glabrata, which is categorized as high priority in the first fungal pathogen priority list of the World Health Organisation released in 2022 for highlighting priority areas for action, including the development of effective therapeutic solution.