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’.

Highlights

  • Emerging fungal pathogens and fungal-like organisms are increasingly threatening natural populations of animals and plants [1]

  • All four lineages are capable of causing disease, a number of differences have been identified between sublineages, such as increased intracellular proliferation rates (IPRs) in VGIIc isolates [5], or an enhanced ability to parasitize host phagocytic cells by VGIIa outbreak isolates

  • These processes are initiated upon engulfment by macrophages, followed by a stress response that triggers cryptococcal mitochondrial tubularization and rapid proliferation of the outbreak strains [19]

Read more

Summary

Introduction

Emerging fungal pathogens and fungal-like organisms are increasingly threatening natural populations of animals and plants [1]. All four lineages are capable of causing disease, a number of differences have been identified between sublineages, such as increased intracellular proliferation rates (IPRs) in VGIIc isolates [5], or an enhanced ability to parasitize host phagocytic cells by VGIIa outbreak isolates. These processes are initiated upon engulfment by macrophages, followed by a stress response that triggers cryptococcal mitochondrial tubularization and rapid proliferation of the outbreak strains [19]. We extend our approach to study the wider population structure and variation among a panel of 64 C. gattii isolates and demonstrate how the methods we detail here are applicable to investigating the genetic determinants that underpin virulence across a wide range of emerging fungal pathogens

Results
Discussion
46. Wartenberg A et al 2014 Microevolution of Candida
52. Springer DJ et al 2014 Cryptococcus gattii VGIII
Findings
31. Bruggemann H et al 2006 Virulence strategies for
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.