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Unlocking the secrets of disease-causing fungus Aspergillus fumigatus

Unlocking the secrets of disease-causing fungus Aspergillus fumigatus
GliT:GFP and GtmA:GFP have enriched vacuolar localization during GT production. GliT:GFP and GtmA:GFP germlings were grown in liquid Czapek-dox medium for 24 h at 37 oC. Representative brightfield, differential interference contrast (DIC), and Cell tracker Blue CMAC (CellTracker Blue CMAC Dye (7-amino-4-chloromethylcoumarin) for vacuolar staining. a The number of GliT:GFP and GtmA:GFP germlings that co-localized with CMAC that was used for vacuolar staining were determined. We have counted three independent experiments with 45 germlings for each strain per experiment (N = 135 germlings) and the results were expressed as the mean values (%) of 3 independent experiments of GFP that co-localizes with CMAC. Yellow arrows indicate the localization of GliT:GFP and GtmA:GFP in magnified images of sub-cellular structures. The p-values were calculated using One-way ANOVA with Tukey’s multiple comparisons test, ****p < 0.0001. Germlings were assigned as positively present in the vacuoles if they have concomitant localization of GliT:GFP or GtmA:GFP in the same vacuole stained by CMC in the same germling. Representative images are shown in (b) and (c). Bars, 5 µm. Source data are provided as a Source Data file. Credit: Nature Communications (2024). DOI: 10.1038/s41467-023-44329-1

An international team of researchers, led by Professor Gustavo Goldman of the University of São Paulo and Maynooth University's Dr. Özgür Bayram, 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 as well as those with 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 .

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. The research team, led by Prof Goldman and Dr. Bayram, 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.

"We have been collaborating with international research teams using our expertise on identification of protein complexes. Our collaboration with Professor Goldman has led to high impact research on revealing the pathogenic traits of Aspergillus fumigatus," Dr. Bayram said.

"Our work not only unravels the complex interplay of molecular actors within Aspergillus fumigatus but also underscores the importance of understanding these mechanisms for potential therapeutic interventions against aspergillosis."

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

"The implications extend beyond mere discovery; there's potential for developing therapeutic approaches," Dr. Bayram said. "For instance, the newfound knowledge might lay the foundation for a treatment targeting aspergillus infections in patients. Such a breakthrough could have for individuals undergoing cancer treatments, organ transplants, those with cystic fibrosis, and those managing (COPD)."

More information: 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

Journal information: Nature Communications

Citation: Unlocking the secrets of disease-causing fungus Aspergillus fumigatus (2024, January 4) retrieved 25 July 2024 from
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