Cryptococcus gattii Genomics and Transcriptomics

Summary

Cryptococcus gattii is an emerging global pathogen that was first recognized in 1970 from Central Africa. Earlier, C. gattii CNS, lung and skin infections were believed to be limited to healthy individuals in tropics and subtropics. Early investigations suggested that these infections were not seen in HIV-AIDS patients. These perspectives might have led to less attention being paid to C. gattii vis-à-vis C. neoformans, which has received maximum attention as an opportunistic pathogen in HIV-AIDS patients. However, many recent reports suggest that C. gattii cryptococcosis is more common in immunocompetent as well as HIV-AIDS patients globally; this is matched by isolations of fungus from more than 50 tree species in temperate and tropical areas. More recently, C. gattii infections and deaths in the Pacific Northwest and Vancouver, Canada have raised public health awareness in North America.

The information on the genome of C. gattii is inadequate and unrepresentative. Currently, draft genome sequences are available for two strains, R265 and WM276, which are MAT, serotype B, genotype VGII/VGI from Canada and Australia, respectively. There is a gap in knowledge about the genomes of VGIII and VGIV strains, serotype C strains, and MATa strains. The geographical representation is inadequate in the absence of strains from California, South America, Asia and Africa. Additional obstacles are: a) reliance on a complex molecular typing schemes, and b) lack of functional analyses (transcriptomics) that can foretell C. gattii response under pathogenic and non-pathogenic conditions.

We propose complete genome sequencing of 12 reference strains by next generation sequencing technology. Transcriptomes of 12 C. gattii strains will also be mapped by RNA-Seq technology. The selection of strains, sampling conditions, analytical strategies and data release plan were designed with input from the 3-Co-PIs, and additional researchers representing global C. gattii community. The project would provide: 1) insight into C. gattii genomes to anchor future research studies, 2) validation of single nucleotide polymorphisms (SNPs) for molecular typing to improve epidemiology studies, and 3) transcript analyses to fast forward the discovery of proteins for diagnostics, drug targets and vaccines. Overall, the project will fill-in important gaps in our knowledge about an important emerging pathogen, accelerate research efforts and translate laboratory findings into tangible public health benefits.

White Paper Access

The initial white paper submitted can be downloaded here. Since white papers are not always approved exactly as submitted, this document may not exactly describe the final form of the project. Please contact gsc@jcvi.org if you have any questions.

All Publications that use data generated and/or are supported by the Sequencing Center at JCVI should acknowledge the sponsor as: This project has been funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract numbers N01-AI30071 and/or HHSN272200900007C.

Investigators and Collaborators

Liliana Losada, PhD

Assistant Professor, JCVI

Brian Wong, PhD

Director, Division of Infectious Diseases, Oregon Health & Science University

Vishnu Chaturvedi, PhD

Director, Mycology Laboratory, Wadsworth Center, New York State Department of Health

K.J. Kwon-Chung, PhD

Chief, Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, NIAID

John Perfect, PhD

Interim Chief, Division of Infectious Diseases, Department of Medicine, School of Medicine, Duke University