# Distinct roles of phytochromes A and B in Aspergillus fumigatus in environmental sensing and pathogenicity

## TL;DR

The study explores how two phytochrome proteins in a harmful fungus affect its ability to cause disease and respond to environmental changes.

## Contribution

The paper reveals FphB as a novel regulatory factor in fungal pathogenicity and secondary metabolism.

## Key findings

- FphA functions as a light and temperature sensor, while FphB suppresses virulence.
- FphB regulates secondary metabolites like neosartoricin B and hexadehydroastechrome.
- FphA and FphB localize to different cellular compartments and form heterodimers.

## Abstract

Phytochromes are red-light receptors that regulate gene expression in response to light and temperature in plants, bacteria, and fungi. In the opportunistic pathogenic fungus Aspergillus fumigatus, two putative phytochromes—FphA and FphB—were characterized to assess any roles in virulence. Spectroscopic analysis of E. coli-expressed proteins showed that FphA is photoconvertible and functionally similar to its A. nidulans ortholog, whereas FphB is photoinactive. Therefore, only FphA could rescue an A. nidulans fphA-deletion mutant. Gene deletion in A. fumigatus revealed that loss of FphA had no effect on virulence, while deletion of FphB—alone or with FphA—significantly increased virulence in a Galleria mellonella infection model. Transcriptomic data linked FphB to the regulation of the neosartoricin B biosynthetic gene cluster and the production of the prenylated nonribosomal peptide hexadehydroastechrome, suggesting a role in regulating secondary metabolism. Localization studies showed FphA at the mitochondria and in nuclei and FphB mainly in the cytoplasm; both proteins form heterodimers in the cytoplasm and in nuclei. These findings suggest that while FphA acts as a light and temperature sensor, FphB modulates virulence and may represent a novel regulatory factor in fungal pathogenicity.

Aspergillus fumigatus is a major pathogen in immunocompromised individuals, showing greater virulence than A. nidulans despite genetic similarities. A key difference is the presence of two phytochrome-like proteins: FphA, a conserved red-light and temperature sensor, and FphB, a photoinactive hybrid histidine kinase. Notably, FphB appears to suppress virulence, suggesting a regulatory role in signaling pathways that govern pathogenicity and secondary metabolism. We propose FphB functions as a signaling hub linking environmental cues to virulence, with its network offering a promising target for antifungal strategies.