Transmission of Hypervirulence traits via sexual reproduction within and between lineages of the human fungal pathogen cryptococcus gattii

Kerstin Voelz, Hansong Ma, Sujal Phadke, Edmond J Byrnes, Pinkuan Zhu, Olaf Mueller, Rhys A Farrer, Daniel A Henk, Yonathan Lewit, Yen-Ping Hsueh, Matthew C Fisher, Alexander Idnurm, Joseph Heitman* (Corresponding Author), Robin C May* (Corresponding Author)

*Corresponding author for this work

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Since 1999 a lineage of the pathogen Cryptococcus gattii has been infecting humans and other animals in Canada and the Pacific Northwest of the USA. It is now the largest outbreak of a life-threatening fungal infection in a healthy population in recorded history. The high virulence of outbreak strains is closely linked to the ability of the pathogen to undergo rapid mitochondrial tubularisation and proliferation following engulfment by host phagocytes. Most outbreaks spread by geographic expansion across suitable niches, but it is known that genetic re-assortment and hybridisation can also lead to rapid range and host expansion. In the context of C. gattii, however, the likelihood of virulence traits associated with the outbreak lineages spreading to other lineages via genetic exchange is currently unknown. Here we address this question by conducting outgroup crosses between distantly related C. gattii lineages (VGII and VGIII) and ingroup crosses between isolates from the same molecular type (VGII). Systematic phenotypic characterisation shows that virulence traits are transmitted to outgroups infrequently, but readily inherited during ingroup crosses. In addition, we observed higher levels of biparental (as opposed to uniparental) mitochondrial inheritance during VGII ingroup sexual mating in this species and provide evidence for mitochondrial recombination following mating. Taken together, our data suggest that hypervirulence can spread among the C. gattii lineages VGII and VGIII, potentially creating novel hypervirulent genotypes, and that current models of uniparental mitochondrial inheritance in the Cryptococcus genus may not be universal.

Original languageEnglish
Article numbere1003771
Number of pages18
JournalPLoS Genetics
Issue number9
Publication statusPublished - 5 Sept 2013

Bibliographical note

This work was financially supported by a Lister Fellowship to Robin C. May, the Medical Research Council (G0601171), the Wellcome Trust (WT088148MF to RCM and WT084616/A/08/Z to MCF), a University of Birmingham Wellcome Trust Institutional Strategic Support Fund award, the National Institute of Health Research Surgical Resconstruction and Microbiology Research Centre, the National Institutes of Health (NIAID AI094364 to AI and NIAID R37 AI39115-15 to JH) and the Chinese Scholarship Council (PZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


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