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Molecular characterization of gliotoxin synthesis in a biofilm model of Aspergillus fumigatus

Summary

Researchers studied how a dangerous fungus called Aspergillus fumigatus produces a toxin called gliotoxin when it forms biofilms, which are organized communities of fungal cells found in human infections. They compared two clinical strains from infected patients and found they produced gliotoxin at different times and in different amounts, despite forming similar biofilm structures. By analyzing which genes were turned on and off, they discovered that one strain rapidly produced toxin early while the other strain produced it more slowly, suggesting different strategies for survival. Understanding these differences could help develop better treatments for serious lung infections caused by this fungus.

Background

Aspergillus fumigatus forms biofilms as an adaptive strategy during infection and activates secondary metabolism to produce metabolites that promote survival in hostile environments. Gliotoxin (GT) is a major secondary metabolite in A. fumigatus that can be detected in serum of patients with invasive aspergillosis and serves as a potential diagnostic biomarker.

Objective

To determine whether the kinetics of gliotoxin production and the molecular mechanisms involved follow a defined pattern during biofilm development using two different clinical strains of A. fumigatus isolated from patients with invasive pulmonary aspergillosis.

Results

Both strains formed biofilms with increased biomass and cellular activity over time. GT was detected mainly in early phases (16-24 h) while bmGT appeared in advanced stages (48-72 h). Two distinct phenotypes emerged: an early producer strain (CM9160) with upregulated biosynthetic genes at 16 h and a late producer strain (Af293) with delayed gene activation. Gene expression patterns correlated with metabolite production kinetics, with gliZ regulatory gene showing critical importance.

Conclusion

A. fumigatus strains demonstrate differential activation of gliotoxin biosynthesis during biofilm development despite forming similar biofilm structures. The distinct phenotypes and molecular profiles suggest differences in pathogenic capacity and adaptation to hostile conditions. The regulatory gene gliZ represents a potential target for modulating secondary metabolism and fungal response to adverse conditions.
  • Published in:Biofilm,
  • Study Type:Experimental Laboratory Study,
  • Source: PMID: 39583991
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