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Pathogenic mucorales: Deciphering their cell wall polysaccharidome and immunostimulatory potential

Summary

Mucormycosis is a dangerous fungal infection that kills many immunocompromised patients. Researchers analyzed the outer layer (cell wall) of three common disease-causing fungi and discovered that their surfaces contain sugar-like molecules that trigger strong inflammatory responses from the immune system. This excessive inflammation may actually contribute to the disease’s severity, suggesting that controlling inflammation alongside antifungal treatment might improve patient outcomes.

Background

Mucormycosis is an emerging infection caused by pathogenic filamentous fungi of the order Mucorales, with significantly high mortality in immunocompromised patients. The fungal cell wall is the first component to interact with the host immune system and its composition varies among species. Understanding cell wall organization and composition of pathogenic Mucorales species is important for managing this life-threatening infection.

Objective

To characterize the cell wall organization and composition of three prevalent pathogenic Mucorales species (Rhizopus arrhizus, Mucor circinelloides, and Lichtheimia corymbifera) and to study their immunomodulatory potential and interactions with human immune cells.

Results

The three Mucorales species showed surface-exposed mannans and distinctly distributed β-1,3-glucan on spores and germ-tubes, with glucose being the major fibrillar polysaccharide. Specific enzymatic digestion revealed that β-1,3-glucan, β-1,6-glucan, and amylase-digestible glucan constitute the fibrillar polysaccharides. Stimulation of immune cells with spores or cell wall polysaccharides resulted in release of pro-inflammatory cytokines regardless of species.

Conclusion

The three Mucorales species analyzed show common and species-specific cell wall compositions. The cell wall polysaccharides are highly pro-inflammatory, suggesting that excessive inflammation may contribute to the immunopathology of mucormycosis. The study provides foundational information for further analysis of cell wall glycobiology and immunobiology of pathogenic Mucorales.
  • Published in:Virulence,
  • Study Type:Experimental Study,
  • Source: PMID: 40621682, DOI: 10.1080/21505594.2025.2528079
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