Cryptococcus gattii VGIII isolates causing infections in HIV/AIDS patients in Southern California: identification of the local environmental source as arboreal.
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2014-08
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Ongoing Cryptococcus gattii outbreaks in the Western United States and Canada illustrate the impact of environmental reservoirs and both clonal and recombining propagation in driving emergence and expansion of microbial pathogens. C. gattii comprises four distinct molecular types: VGI, VGII, VGIII, and VGIV, with no evidence of nuclear genetic exchange, indicating these represent distinct species. C. gattii VGII isolates are causing the Pacific Northwest outbreak, whereas VGIII isolates frequently infect HIV/AIDS patients in Southern California. VGI, VGII, and VGIII have been isolated from patients and animals in the Western US, suggesting these molecular types occur in the environment. However, only two environmental isolates of C. gattii have ever been reported from California: CBS7750 (VGII) and WM161 (VGIII). The incongruence of frequent clinical presence and uncommon environmental isolation suggests an unknown C. gattii reservoir in California. Here we report frequent isolation of C. gattii VGIII MATα and MATa isolates and infrequent isolation of VGI MATα from environmental sources in Southern California. VGIII isolates were obtained from soil debris associated with tree species not previously reported as hosts from sites near residences of infected patients. These isolates are fertile under laboratory conditions, produce abundant spores, and are part of both locally and more distantly recombining populations. MLST and whole genome sequence analysis provide compelling evidence that these environmental isolates are the source of human infections. Isolates displayed wide-ranging virulence in macrophage and animal models. When clinical and environmental isolates with indistinguishable MLST profiles were compared, environmental isolates were less virulent. Taken together, our studies reveal an environmental source and risk of C. gattii to HIV/AIDS patients with implications for the >1,000,000 cryptococcal infections occurring annually for which the causative isolate is rarely assigned species status. Thus, the C. gattii global health burden could be more substantial than currently appreciated.
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Springer, DJ, RB Billmyre, EE Filler, K Voelz, R Pursall, PA Mieczkowski, RA Larsen, FS Dietrich, et al. (2014). Cryptococcus gattii VGIII isolates causing infections in HIV/AIDS patients in Southern California: identification of the local environmental source as arboreal. PLoS Pathog, 10(8). p. e1004285. 10.1371/journal.ppat.1004285 Retrieved from https://hdl.handle.net/10161/9025.
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Fred Samuel Dietrich
My laboratory is interested in fungal genomics.
In particular we use genomic sequencing of fungal strains and species in comparative analysis. Starting with the sequencing of Saccharomyces cerevisiae strain S288C, I have been involved in the genome sequencing and annotation of Ashbya gossypii, Cryptococcus neoformans var. grubii and ~100 additional S. cerevisiae strains. We currently use Illumina paired end and mate paired sequencing, as this is at presently the most cost effective widely used technology capable of generating high accuracy, zero gap whole genome sequences. The 100-genomes S. cerevisiae data as well as the fully updated fully annotated A. gossypii sequence (Genbank numbers AE016814-AE016820), which spans all seven chromosomes from telomere to telomere, were generated using Illumina data. In my laboratory we strive to utilize comparative genomics data to understand aspects of basic fungal biology. Some of our specific areas of interest are filamentous growth, mapping of complex traits, horizontal gene transfer, and identification of RNA coding genes. This work involves a combination of experimental work and bioinformatics analysis. Research in S. cerevisiae has greatly benefitted from an accurate, annotated S. cerevisiae reference genome, and that research into the tremendous diversity in this organism will similarly benefit from the availability of a large number of accurate, fully annotated genome sequences. The use of genomic information to better understand the biology of these organisms, and this is what students in my laboratory generally work on.
What is the set of genes found in a pathogenic fungus such as Cryptococcus?
Our interest in this human pathogen is to expand beyond looking at one isolate and to investigate the diversity in the population. Are there genes found in some Cryptococcus neoformans isolates but not in others? Are there regions of the genome or individual genes which are highly diverged between Cryptococcus isolates? Efforts are now underway at Stanford University to sequence the genome of the JEC21 strain of Cryptococcus. This is a strain that has been agreed upon by the community of Cryptococcus researchers as a reference strain. Obtaining the DNA sequence of this strain is only the start however. From that sequence identifying the complete set of genes will be a considerable challenge requiring both bioinformatic as well as experimental tools. While this work on gene identification is going on we plan on addressing the question of how much do other Cryptococcus isolates differ from JEC21.
What is the set of genes in humans?
The complete DNA sequence of human and mouse will become available soon. This does not mean that we will know the complete set of human or mouse genes. Our current state of knowledge does not allow us to accurately predict human genes directly from DNA sequence. We are interested in applying to the human genome some of the experimental and bioinformatic tools we are developing and utilizing in fungal systems.
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