# A small heat shock protein Fmp28 influences virulence by regulating Als3 expression via the cAMP-PKA signaling pathway in Candida albicans

## TL;DR

This study shows that a small heat shock protein called Fmp28 helps Candida albicans become more harmful by controlling another protein, Als3, through a specific signaling pathway.

## Contribution

The study identifies Fmp28 as a novel small heat shock protein that regulates virulence via the cAMP-PKA pathway in Candida albicans.

## Key findings

- Fmp28 deletion impairs growth, adhesion, biofilm formation, and virulence in Candida albicans.
- Als3 overexpression rescues the virulence defects caused by Fmp28 deletion.
- Fmp28 influences the cAMP-PKA pathway and ATP levels, which are critical for virulence.

## Abstract

Small heat shock proteins are evolutionarily conserved molecular chaperones with diverse cellular roles. However, our understanding of their functions in pathogenic microorganisms remains limited. In this study, we identified and characterized Fmp28, a novel small heat shock protein that enhances virulence in Candida albicans, and explored its regulatory mechanism. The expression of Fmp28 was significantly upregulated at both transcriptional and translational levels when C. albicans was subjected to physiological temperature (37°C), osmotic stress, or cell wall stress. Deletion of Fmp28 significantly impaired growth, adhesion, biofilm formation, invasive growth, and virulence at physiological temperature (37°C), respectively. Transcriptome analysis identified Als3 as a key downstream target of Fmp28. Notably, Als3 overexpression substantially rescued the impairments in adhesion, biofilm formation, invasion, and virulence caused by FMP28 deletion. Deletion of FMP28 also led to downregulated expression of genes in the cAMP-PKA pathway, as well as reduced intracellular ATP and cAMP levels. By adding exogenous cAMP analogs, the adhesion and biofilm formation in the fmp28Δ/Δ mutant could be partially restored. In conclusion, the findings in this study demonstrated that Fmp28 maintained C. albicans virulence at physiological temperature by regulating Als3 expression through the cAMP-PKA signaling pathway, establishing Fmp28 as a potential therapeutic target for treating C. albicans infections.

We have identified Fmp28 as a novel small heat shock protein that is essential for C. albicans adaptation to diverse stresses and full virulence. Furthermore, we elucidated that Fmp28 interacts with Qcr10 on the mitochondria to maintain the concentration of ATP, promoting virulence by regulating Als3 expression via the cAMP-PKA pathway, providing new insights into how C. albicans maintains its stress adaptation and full virulence at a physiological temperature of 37°C. Our findings established Fmp28 as a potential therapeutic target for treating C. albicans infections, which is particularly relevant, given the rising concern about antifungal resistance.