Distinct roles of phytochromes A and B in <i>Aspergillus fumigatus</i> in environmental sensing and pathogenicity

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 <i>Aspergillus fumigatus</i>, two putative phytochromes-FphA and FphB-were characterized to assess any roles in virulence. Spectroscopic analysis of <i>E. coli</i>-expressed proteins showed that FphA is photoconvertible and functionally similar to its <i>A. nidulans</i> ortholog, whereas FphB is photoinactive. Therefore, only FphA could rescue an <i>A. nidulans fphA</i>-deletion mutant. Gene deletion in <i>A. fumigatus</i> revealed that loss of FphA had no effect on virulence, while deletion of FphB-alone or with FphA-significantly increased virulence in a <i>Galleria mellonella</i> 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.IMPORTANCE<i>Aspergillus fumigatus</i> is a major pathogen in immunocompromised individuals, showing greater virulence than <i>A. nidulans</i> 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.