Pathogen-derived extracellular vesicles mediate virulence in the fatal human pathogen Cryptococcus gattii

Area of Science:

• Mycology
• Infectious Diseases
• Cell Biology

Background:

• The Pacific Northwest outbreak of cryptococcosis, caused by Cryptococcus gattii, is a major cause of life-threatening fungal infections in healthy individuals.
• The outbreak lineage exhibits rapid growth within human white blood cells via a 'division of labour' mechanism, where some fungal cells remain dormant to support others.

Purpose of the Study:

• To investigate the mechanism of long-distance communication in Cryptococcus gattii virulence.
• To determine if extracellular vesicles mediate the 'division of labour' phenomenon.

Main Methods:

• Isolation and characterization of extracellular vesicles from virulent Cryptococcus gattii strains.
• Uptake studies of these vesicles by host macrophages.
• Analysis of intracellular fungal growth following vesicle uptake.

Main Results:

• Extracellular vesicles trigger pathogenic 'division of labour' over large cellular distances.
• Vesicles are taken up by host macrophages and trafficked to the phagosome.
• Uptake of vesicles leads to rapid intracellular growth of non-outbreak fungal cells, enhancing virulence.

Conclusions:

• Extracellular vesicles mediate long-distance pathogen-to-pathogen communication in Cryptococcus gattii.
• This communication mechanism controls complex virulence phenotypes, representing a novel target for antifungal strategies.