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

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Pathogen-derived extracellular vesicles mediate virulence in the fatal human pathogen Cryptococcus gattii. / Bielska, Ewa; Sisquella, Marta Arch; Aldeieg, Maha; Birch, Charlotte; O'Donoghue, Eloise J; May, Robin C.

In: Nature Communications, Vol. 9, 1556 , 19.04.2018.

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Bielska, Ewa ; Sisquella, Marta Arch ; Aldeieg, Maha ; Birch, Charlotte ; O'Donoghue, Eloise J ; May, Robin C. / Pathogen-derived extracellular vesicles mediate virulence in the fatal human pathogen Cryptococcus gattii. In: Nature Communications. 2018 ; Vol. 9.

Bibtex

@article{95e674d016ad4060b91ac5eb02cd0bb2,
title = "Pathogen-derived extracellular vesicles mediate virulence in the fatal human pathogen Cryptococcus gattii",
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.",
author = "Ewa Bielska and Sisquella, {Marta Arch} and Maha Aldeieg and Charlotte Birch and O'Donoghue, {Eloise J} and May, {Robin C}",
year = "2018",
month = apr,
day = "19",
doi = "10.1038/s41467-018-03991-6",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer",

}

RIS

TY - JOUR

T1 - Pathogen-derived extracellular vesicles mediate virulence in the fatal human pathogen Cryptococcus gattii

AU - Bielska, Ewa

AU - Sisquella, Marta Arch

AU - Aldeieg, Maha

AU - Birch, Charlotte

AU - O'Donoghue, Eloise J

AU - May, Robin C

PY - 2018/4/19

Y1 - 2018/4/19

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-018-03991-6

DO - 10.1038/s41467-018-03991-6

M3 - Article

C2 - 29674675

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 1556

ER -