# Oxidoreductase gene fabG contributes to fungal development, cell wall integrity, and virulence in Aspergillus fumigatus

## TL;DR

The fabG gene in Aspergillus fumigatus is crucial for growth, stress adaptation, and virulence, making it a potential target for antifungal treatments.

## Contribution

This study identifies fabG as a novel regulator of cell wall integrity and redox homeostasis in A. fumigatus.

## Key findings

- fabG knockout strains show reduced growth, virulence, and caspofungin sensitivity.
- ΔfabG leads to increased ROS, decreased SOD activity, and heightened macrophage-induced killing.
- fabG modulates cell wall thickening and stress tolerance, but not in response to caspofungin or rapamycin.

## Abstract

Aspergillus fumigatus, a major cause of invasive aspergillosis, relies on oxidoreductases for stress adaptation. The role of the oxidoreductase gene fabG in fungal physiology and virulence remains unclear. This study aims to investigate the function of fabG in regulating A. fumigatus growth, virulence, redox homeostasis, and cell wall integrity (CWI). fabG knockout (ΔfabG) and complemented strains were constructed via homologous recombination. Phenotypic assays evaluated hyphal growth, virulence in Galleria mellonella, and antifungal susceptibility. Transcriptomic profiling, cell wall composition analysis (chitin/β-glucan), biochemical assays (superoxide dismutase [SOD] activity, reactive oxygen species [ROS] levels, and stress tolerance), and macrophage co-culture experiments (phagocytosis/killing) were performed. CWI-related gene expression was assessed under caspofungin/rapamycin treatment. ΔfabG showed inhibited hyphal growth, reduced virulence, and decreased caspofungin sensitivity. Transcriptomics revealed altered oxidoreductase and mitogen-activated protein kinase signaling genes. Cell wall thickening (increased chitin) and enhanced tolerance to cell wall stressors indicated CWI activation. ΔfabG exhibited decreased SOD activity, elevated ROS, reduced stress tolerance, and increased susceptibility to macrophage killing. CWI-related gene expression was unchanged under caspofungin/rapamycin. fabG critically regulates A. fumigatus growth, environmental adaptation, and virulence by modulating CWI and redox homeostasis, highlighting its potential as an antifungal target.

Aspergillus fumigatus is a harmful fungus that can cause severe and often deadly infections in people with weakened immune systems. Understanding how this fungus adapts to stress and causes disease is crucial for developing new treatments. Our study reveals that the gene fabG plays a vital role in regulating the growth, stress response, and virulence of A. fumigatus. When FabG is missing, the fungus becomes less able to grow, resists environmental stresses poorly, and is less harmful to infected hosts. This gene controls the fungus’s ability to maintain internal balance during oxidative stress and strengthens its cell wall, a protective structure. Since FabG is critical for the fungus’s survival and virulence, it could be a promising target for new antifungal drugs. By blocking fabG, we might be able to develop more effective treatments against this dangerous pathogen.