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Nat Commun. 2018 Apr 19;9(1):1556. doi: 10.1038/s41467-018-03991-6.

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

Author information

1
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. ewabielska@mail.com.
2
Institut d' Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Crta de Can Ruti s/n, Badalona, 08916, Catalonia, Spain.
3
School of Biological Sciences, University of Reading, Knight Building, Whiteknights Campus, Reading, RG6 6AJ, UK.
4
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
5
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. r.c.may@bham.ac.uk.

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.

PMID:
29674675
PMCID:
PMC5908794
DOI:
10.1038/s41467-018-03991-6
[Indexed for MEDLINE]
Free PMC Article

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