Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii

Rhys A Farrer (Corresponding Author), Kerstin Voelz, Daniel A Henk, Simon A Johnston, Matthew C Fisher, Robin C May, Christina A Cuomo

Research output: Contribution to journalArticle

12 Citations (Scopus)
5 Downloads (Pure)

Abstract

Emerging fungal pathogens cause an expanding burden of disease across the animal kingdom, including a rise in morbidity and mortality in humans. Yet, we currently have only a limited repertoire of available therapeutic interventions. A greater understanding of the mechanisms of fungal virulence and of the emergence of hypervirulence within species is therefore needed for new treatments and mitigation efforts. For example, over the past decade, an unusual lineage of Cryptococcus gattii, which was first detected on Vancouver Island, has spread to the Canadian mainland and the Pacific Northwest infecting otherwise healthy individuals. The molecular changes that led to the development of this hypervirulent cryptococcal lineage remain unclear. To explore this, we traced the history of similar microevolutionary events that can lead to changes in host range and pathogenicity. Here, we detail fine-resolution mapping of genetic differences between two highly related Cryptococcus gattii VGIIc isolates that differ in their virulence traits (phagocytosis, vomocytosis, macrophage death, mitochondrial tubularization and intracellular proliferation). We identified a small number of single site variants within coding regions that potentially contribute to variations in virulence. We then extended our methods across multiple lineages of C. gattii to study how selection is acting on key virulence genes within different lineages.

This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.

Original languageEnglish
Article number20160021
Number of pages11
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume371
Issue number1709
Early online date24 Oct 2016
DOIs
Publication statusPublished - 5 Dec 2016

Fingerprint

Cryptococcus gattii
Metagenomics
virulence
Fungi
Virulence
genomics
Animals
fungus
fungi
Macrophages
Pathogens
Ecosystems
Genes
Health
ecosystem resilience
burden of disease
health foods
Northwestern United States
host range
pathogenicity

Keywords

  • Cryptococcus gatti
  • microevolution
  • mitochondrial tubularization
  • intracellular proliferation

Cite this

Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii. / Farrer, Rhys A (Corresponding Author); Voelz, Kerstin; Henk, Daniel A; Johnston, Simon A; Fisher, Matthew C; May, Robin C; Cuomo, Christina A.

In: Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 371, No. 1709, 20160021, 05.12.2016.

Research output: Contribution to journalArticle

Farrer, Rhys A ; Voelz, Kerstin ; Henk, Daniel A ; Johnston, Simon A ; Fisher, Matthew C ; May, Robin C ; Cuomo, Christina A. / Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii. In: Philosophical Transactions of the Royal Society B: Biological Sciences. 2016 ; Vol. 371, No. 1709.
@article{5c1f1f5cc64b46eabd908a607244e5ba,
title = "Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii",
abstract = "Emerging fungal pathogens cause an expanding burden of disease across the animal kingdom, including a rise in morbidity and mortality in humans. Yet, we currently have only a limited repertoire of available therapeutic interventions. A greater understanding of the mechanisms of fungal virulence and of the emergence of hypervirulence within species is therefore needed for new treatments and mitigation efforts. For example, over the past decade, an unusual lineage of Cryptococcus gattii, which was first detected on Vancouver Island, has spread to the Canadian mainland and the Pacific Northwest infecting otherwise healthy individuals. The molecular changes that led to the development of this hypervirulent cryptococcal lineage remain unclear. To explore this, we traced the history of similar microevolutionary events that can lead to changes in host range and pathogenicity. Here, we detail fine-resolution mapping of genetic differences between two highly related Cryptococcus gattii VGIIc isolates that differ in their virulence traits (phagocytosis, vomocytosis, macrophage death, mitochondrial tubularization and intracellular proliferation). We identified a small number of single site variants within coding regions that potentially contribute to variations in virulence. We then extended our methods across multiple lineages of C. gattii to study how selection is acting on key virulence genes within different lineages.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.",
keywords = "Cryptococcus gatti, microevolution, mitochondrial tubularization, intracellular proliferation",
author = "Farrer, {Rhys A} and Kerstin Voelz and Henk, {Daniel A} and Johnston, {Simon A} and Fisher, {Matthew C} and May, {Robin C} and Cuomo, {Christina A}",
note = "Electronic supplementary material is available online at http://dx.doi.org/10.6084/m9.figshare.c.3493062. Data accessibility. The genome sequence and feature files for C. gattii R265 are available from GenBank (project accession number AAFP01000000). All sequencing data are available from the SRA project accession SRP017762, and along with the phenotypic data, described in previous studies [16,24,52]. Funding. This work was financially supported by a Lister Fellowship to R.C.M., the Medical Research Council (G0601171), the Wellcome Trust (WT088148MF) and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) ERC Grant agreement no. 614562. R.A.F. is supported by the Wellcome Trust. This project was supported in part by NIAID grant no. U19AI110818 to the Broad Institute. This work was also supported by independent research funded by the National Institute of Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the NIH or the Department of Health. Acknowledgements. We thank Arturo Casadevall for providing the 18B7 antibody used in this study and Hannah Larner for the genomic library preparation.",
year = "2016",
month = "12",
day = "5",
doi = "10.1098/rstb.2016.0021",
language = "English",
volume = "371",
journal = "Philosophical Transactions of the Royal Society B: Biological Sciences",
issn = "0962-8436",
publisher = "ROYAL SOC CHEMISTRY",
number = "1709",

}

TY - JOUR

T1 - Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii

AU - Farrer, Rhys A

AU - Voelz, Kerstin

AU - Henk, Daniel A

AU - Johnston, Simon A

AU - Fisher, Matthew C

AU - May, Robin C

AU - Cuomo, Christina A

N1 - Electronic supplementary material is available online at http://dx.doi.org/10.6084/m9.figshare.c.3493062. Data accessibility. The genome sequence and feature files for C. gattii R265 are available from GenBank (project accession number AAFP01000000). All sequencing data are available from the SRA project accession SRP017762, and along with the phenotypic data, described in previous studies [16,24,52]. Funding. This work was financially supported by a Lister Fellowship to R.C.M., the Medical Research Council (G0601171), the Wellcome Trust (WT088148MF) and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) ERC Grant agreement no. 614562. R.A.F. is supported by the Wellcome Trust. This project was supported in part by NIAID grant no. U19AI110818 to the Broad Institute. This work was also supported by independent research funded by the National Institute of Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the NIH or the Department of Health. Acknowledgements. We thank Arturo Casadevall for providing the 18B7 antibody used in this study and Hannah Larner for the genomic library preparation.

PY - 2016/12/5

Y1 - 2016/12/5

N2 - Emerging fungal pathogens cause an expanding burden of disease across the animal kingdom, including a rise in morbidity and mortality in humans. Yet, we currently have only a limited repertoire of available therapeutic interventions. A greater understanding of the mechanisms of fungal virulence and of the emergence of hypervirulence within species is therefore needed for new treatments and mitigation efforts. For example, over the past decade, an unusual lineage of Cryptococcus gattii, which was first detected on Vancouver Island, has spread to the Canadian mainland and the Pacific Northwest infecting otherwise healthy individuals. The molecular changes that led to the development of this hypervirulent cryptococcal lineage remain unclear. To explore this, we traced the history of similar microevolutionary events that can lead to changes in host range and pathogenicity. Here, we detail fine-resolution mapping of genetic differences between two highly related Cryptococcus gattii VGIIc isolates that differ in their virulence traits (phagocytosis, vomocytosis, macrophage death, mitochondrial tubularization and intracellular proliferation). We identified a small number of single site variants within coding regions that potentially contribute to variations in virulence. We then extended our methods across multiple lineages of C. gattii to study how selection is acting on key virulence genes within different lineages.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.

AB - Emerging fungal pathogens cause an expanding burden of disease across the animal kingdom, including a rise in morbidity and mortality in humans. Yet, we currently have only a limited repertoire of available therapeutic interventions. A greater understanding of the mechanisms of fungal virulence and of the emergence of hypervirulence within species is therefore needed for new treatments and mitigation efforts. For example, over the past decade, an unusual lineage of Cryptococcus gattii, which was first detected on Vancouver Island, has spread to the Canadian mainland and the Pacific Northwest infecting otherwise healthy individuals. The molecular changes that led to the development of this hypervirulent cryptococcal lineage remain unclear. To explore this, we traced the history of similar microevolutionary events that can lead to changes in host range and pathogenicity. Here, we detail fine-resolution mapping of genetic differences between two highly related Cryptococcus gattii VGIIc isolates that differ in their virulence traits (phagocytosis, vomocytosis, macrophage death, mitochondrial tubularization and intracellular proliferation). We identified a small number of single site variants within coding regions that potentially contribute to variations in virulence. We then extended our methods across multiple lineages of C. gattii to study how selection is acting on key virulence genes within different lineages.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.

KW - Cryptococcus gatti

KW - microevolution

KW - mitochondrial tubularization

KW - intracellular proliferation

U2 - 10.1098/rstb.2016.0021

DO - 10.1098/rstb.2016.0021

M3 - Article

VL - 371

JO - Philosophical Transactions of the Royal Society B: Biological Sciences

JF - Philosophical Transactions of the Royal Society B: Biological Sciences

SN - 0962-8436

IS - 1709

M1 - 20160021

ER -