# Multi-Omics Analyses Reveal the Antifungal Mechanism of Phenazine-1-Carboxylic Acid Against Pseudogymnoascus destructans

## TL;DR

This study explores how phenazine-1-carboxylic acid fights the fungus causing white-nose syndrome in bats by disrupting cell structures and causing damage.

## Contribution

The study reveals the antifungal mechanism of PCA against Pseudogymnoascus destructans using multi-omics approaches.

## Key findings

- PCA disrupts cell wall organization and increases membrane permeability in P. destructans.
- PCA induces oxidative stress, DNA damage, and apoptosis in the fungus.
- Transcriptomic and metabolomic analyses show PCA affects metabolism and virulence factors.

## Abstract

White-nose syndrome (WNS) is an infectious disease of bats caused by the psychrophilic fungus Pseudogymnoascus destructans. Phenazine-1-carboxylic acid (PCA) is a microbial secondary metabolite with broad-spectrum antifungal activity. Previous studies show that PCA suppresses the growth of P. destructans at low concentrations, yet its mechanism remains unclear. Here, we evaluated the in vitro antifungal activity of PCA. We then investigated its potential mechanism using physiological and biochemical assays, as well as integrated transcriptomic and metabolomic analyses. PCA showed effective antifungal activity against P. destructans (EC50 = 32.9 μg/mL). Physiological and biochemical assays indicated that PCA perturbed cell wall organization and increased membrane permeability, leading to leakage of intracellular contents. It also induced oxidative stress, DNA damage, and apoptosis. Multi-omics integration revealed that PCA markedly perturbed cell wall and membrane metabolism, virulence factor expression, and energy metabolism. It provoked oxidative stress while downregulating genes involved in the cell cycle, DNA replication, and repair. Together, these findings delineate the inhibitory effects of PCA on P. destructans in vitro, provide initial mechanistic insights into its antifungal action, and suggest that PCA merits further evaluation as a possible component of environmentally compatible strategies for WNS management.