Cryptococcus

Event Date: 
Wednesday, May 28, 2014 - 19:00 - 20:00
Institution: 
USyd
Title: 

Population genetics and evolution of Cryptococcus gattii : an environmental pathogen

Abstract: 

The yeast species Cryptococcus neoformans and C. gattii cause cryptococosis in humans and a range of animal. Although research on Cryptococcus is generally structured in terms of its importance as a fungal pathogen, human infection is accidental and the fungus mostly lives as an environmental saprotroph. C. neoformans and C. gattii each comprise a number of distinct molecular genotypes that vary in their ecology, their geographic distribution, and various virulence-associated phenotypes. In particular, C. gattii molecular type VGII is responsible for outbreaks that have expanded the fungus beyond its normal geographic range. Our interests lie in understanding the ecology and evolution of C. gattii in the environment, and how these relate to its ability to cause disease. We have found the level of sexual recombination varies by molecular type, and that while in general C. gattii population structure is sexual, this is punctuated by periodic clonal lineages that may be associated with disease outbreaks. Here we refine our analysis using MLST data, haplotype networks and coalesence theory. We find the level of diversity within genotypes to be highly constrained and comparable to some recently evolved plant pathogens, and evidence for purifying selection at the master regulator of mating type. Comparison with other fungi that are causing major outbreaks suggests C. gattii outbreaks may be due to a “perfect storm”, where range expansion and elevated transmission combined with high virulence bring the fungus to new areas with deadly consequences. 

Metagenomics has been a hot topic at JAMS in 2011. Playing to this popular theme, Thomas Jeffries of the University of Technology, Sydney opened the final meeting for the year with his metagenomic analysis of taxonomic and functional patterns in South Australia's hypersaline Coorong Lagoon. Thomas and colleagues found shifts in the abundance of cyanobacteria and Archaea linked to a salinity and nutrient gradient along the lagoon, as well as a shift in the abundance of genes related to salinity tolerance and photosynthesis. Surprisingly, despite the extreme range of environmental factors within Coorong, they found these patterns were dwarfed when the lagoon samples were placed in a global context, which showed substrate - in this case, solid or fluid - had a greater influence on taxonomic profiles. Thomas's work shows the importance of scale in the relationship between a microbial community and its environment.

Event Date: 
Wednesday, November 30, 2011 - 18:15 - 18:30
Institution: 
University of Sydney
Title: 

The fungal secretome and virulence: analysis of the proteins secreted by Cryptococcus gattii strains with different virulence profiles.

Abstract: 
Cryptococcus gattii is a ubiquitous environmental yeast-like fungus capable of causing disease in a wide range of animal hosts. In humans, disease progression begins after inhalation of the infectious propagule leading to infection of the lung. The infective yeast cells can then disseminate to the central nervous system, resulting in meningoencephalitis, which can be fatal if left untreated.

Closely related strains of C. gattii exhibit significantly different degrees of virulence in the mammalian host. Fungi utilize absorbtive nutrition and produce a range of secreted degrative enzymes, and as these may invoke a host response, the fungal secretome is likely to be very important in modulating the host-pathogen interaction. In this study, we compare the secretomes of two C. gattii strains, one categorized as hypervirulent (R265) and the other exhibiting low-level virulence (R272). C. gattii was grown under conditions designed to be as similar as possible to those encountered in vivo. Secreted proteins were captured from the culture supernatant by re-circulating across ProteominerTM beads using a closed peristaltic pump system. Concentrated protein was analysed via 1D nanoLC-MS/MS. A total of 27 proteins were identified with only four protein identifications being shared by both strains. The secretome of R265 primarily included uncharacterized proteins containing catalytic cores with roles in carbohydrate degradation as well as the antioxidant superoxide dismutase and a GTPase. R272 secreted a more diverse set of proteins including enolase and transaldolase, enzymes canonically involved in glycolysis and the pentose phosphate pathway respectively, but both also described as fungal allergens that bind IgE.

This work indicates that very different cohorts of proteins are secreted by closely related strains of C. gattii exhibiting different levels of virulence. By enhancing our understanding of the fungal secretome and unraveling these differences it may suggest novel therapeutic strategies or help devise diagnostic markers predicting for disease progression.
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