Pathogenic mucorales: Deciphering their cell wall polysaccharidome and immunostimulatory potential

Area of Science:

• Mycology
• Immunology
• Medical Mycology

Background:

• Mucormycosis, a serious fungal infection, has high mortality, especially in immunocompromised individuals.
• The fungal cell wall is a key interaction point with the host immune system.
• Understanding Mucorales cell wall composition is crucial for addressing mucormycosis.

Purpose of the Study:

• To characterize the cell wall organization and composition of three prevalent Mucorales species: Rhizopus arrhizus, Mucor circinelloides, and Lichtheimia corymbifera.
• To investigate the immunomodulatory potential of these fungal cell walls.

Main Methods:

• Microscopic staining and lectin/immunolabeling to identify surface polysaccharides.
• Gas chromatography to analyze cell wall composition.
• Enzymatic digestion and chromatography to characterize fibrillar polysaccharides.
• Stimulation of human immune cells (PBMCs and THP-1) with fungal spores and cell wall extracts.

Main Results:

• Surface-exposed mannans were found on spores and germ-tubes; β-1,3-glucan was distinct on germ-tubes.
• Glucose polymer was the major fibrillar polysaccharide across species; amorphous components varied.
• β-1,3-glucan, β-1,6-glucan, and amylase-digestible glucans were identified as fibrillar polysaccharides.
• Fungal spores and cell wall extracts induced pro-inflammatory cytokine release from human immune cells.

Conclusions:

• The studied Mucorales species exhibit both common and species-specific cell wall compositions.
• Mucorales cell wall polysaccharides are potent inducers of pro-inflammatory responses.
• Excessive inflammation driven by cell wall components may contribute to mucormycosis immunopathology.