Unlocking the secrets of disease-causing fungus Aspergillus fumigatus

An international team of researchers  has unveiled ground-breaking findings on Aspergillus fumigatus, which can cause deadly disease in humans.

The saprophytic fungus is notorious for causing a spectrum of human diseases, known collectively as aspergillosis, in individuals undergoing cancer treatments and organ transplants as well as those with cystic fibrosis and chronic obstructive pulmonary disease.

The human pathogen is at the forefront of the World Health Organization's priority list, ranking as the most significant among health-threatening fungal pathogens.

The study, published in Nature Communications, sheds light on the intricate mechanisms underlying the virulence of Aspergillus fumigatus, specifically focusing on the crucial role of mycotoxin gliotoxin production. Gliotoxin helps this fungus to kill human immune cells including macrophages and neutrophiles.

Aspergillus fumigatus relies on a delicate balance in regulating gliotoxin production to prevent excess and mitigate toxicity to the fungus itself. 

Researchers identified the pivotal roles played by GliT oxidoreductase and GtmA methyltransferase in the self-protection mechanism of gliotoxin. Both enzymes were observed to be localized in the cytoplasm and vacuoles during gliotoxin production.

The study demonstrates the pivotal role of the Mitogen-Activated Protein kinase MpkA in both gliotoxin production and self-protection. MpkA was found to physically interact with GliT and GtmA, influencing their regulation and subsequent presence in vacuoles—an association not previously made or demonstrated in relation to gliotoxin production.

The researchers emphasize the significance of compartmentalization of cellular events and the orchestrated interplay of these key enzymes for the effective production of gliotoxin and the self-defense mechanism of the fungus.

The findings contribute significantly to the understanding of fungal pathogenesis and open avenues for targeted approaches in combating diseases caused by Aspergillus fumigatus.

Patrícia Alves de Castro et al, Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection, Nature Communications (2024). DOI: 10.1038/s41467-023-44329-1