# Pseudolaric Acid B Combats Drug‐Resistant Candida albicans Infection via Dual‐Action Mechanisms of Direct Antifungals and Vaginal Microbiota Restoration

## TL;DR

Pseudolaric acid B treats drug-resistant yeast infections by killing the fungus and restoring healthy vaginal bacteria.

## Contribution

PAB is shown to combat Candida albicans through dual mechanisms: direct antifungal action and microbiota restoration.

## Key findings

- PAB inhibits biofilm formation and reduces ergosterol biosynthesis by downregulating ERG11.
- PAB restores vaginal microbiota and reduces inflammation in a mouse model of vaginitis.
- PAB shows superior therapeutic efficacy compared to conventional antibiotics in treating Candida infections.

## Abstract

Candidal vaginitis is a prevalent inflammatory condition of the reproductive tract that has a substantial impact on women's health. Conventional antibiotic therapy frequently results in recurrence due to the non‐selective elimination of vaginal microbiota and subsequent dysbiosis. In order to overcome this limitation, the focus was directed towards traditional Chinese medicine, which has antimicrobial properties and it was here that pseudolaric acid B (PAB) was identified as a promising active monomer through the utilisation of virtual screening and bioinformatics approaches. In vitro experiments confirmed that PAB inhibits biofilm formation, reduces ergosterol biosynthesis by downregulating the key gene ERG11, and enhances fungal cell membrane permeability, ultimately resulting in fungal cell death. In vivo studies in a mouse model of
Candida albicans
‐induced vaginitis demonstrated that PAB exhibits superior therapeutic efficacy compared to conventional antibiotics. This is characterised by the restoration of normal tissue architecture, a reduction in inflammatory responses and a significant enrichment of beneficial vaginal microbiota as revealed by 16S rRNA sequencing. Collectively, these results highlight PAB as a promising dual‐mechanism antifungal agent which acts, at least in part, by disrupting fungal ergosterol biosynthesis and directly eradicating pathogens, while restoring vaginal microecological homeostasis.

We propose a novel therapeutic approach against fungal infection: Pseudolaric acid B directly eradicates
C. albicans
via Erg11 inhibition and uniquely, restores vaginal microecological homeostasis by promoting probiotic lactobacilli, addressing both the pathogen and the dysbiotic environment.