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

Ewa Bielska (), Marta Arch Sisquella, Maha Aldeieg, Charlotte Birch, Eloise J. O’Donoghue and Robin C. May ()
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Ewa Bielska: University of Birmingham
Marta Arch Sisquella: Institut d’ Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP)
Maha Aldeieg: University of Reading
Charlotte Birch: University of Birmingham
Eloise J. O’Donoghue: University of Birmingham
Robin C. May: University of Birmingham

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: Abstract The Pacific Northwest outbreak of cryptococcosis, caused by a near-clonal lineage of the fungal pathogen Cryptococcus gattii, represents the most significant cluster of life-threatening fungal infections in otherwise healthy human hosts currently known. The outbreak lineage has a remarkable ability to grow rapidly within human white blood cells, using a unique ‘division of labour’ mechanism within the pathogen population, where some cells adopt a dormant behaviour to support the growth of neighbouring cells. Here we demonstrate that pathogenic ‘division of labour’ can be triggered over large cellular distances and is mediated through the release of extracellular vesicles by the fungus. Isolated vesicles released by virulent strains are taken up by infected host macrophages and trafficked to the phagosome, where they trigger the rapid intracellular growth of non-outbreak fungal cells that would otherwise be eliminated by the host. Thus, long distance pathogen-to-pathogen communication via extracellular vesicles represents a novel mechanism to control complex virulence phenotypes in Cryptococcus gattii and, potentially, other infectious species.

Date: 2018
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DOI: 10.1038/s41467-018-03991-6

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