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Selection of optimal host strain for molecular pathogenesis studies on Cryptococcus gattii
Sudha Chaturvedi1, Ping Ren, Srinivas D Narasipura
1Mycology Laboratory, Wadsworth Center, New York State Department of Health, Albany, NY 12208-2002, USA. schaturv@wadsworth.org
Abstract:
Encapsulated yeast, Cryptococcus gattii (Cg) is a primary and emerging fungal pathogen in North America. It has a predilection for invading the central nervous system of both healthy and immunocompromised humans and animals. Recently, we initiated molecular pathogenesis studies in Cg strain NIH444 (ATCC 32609). In this report, we compared the biology and pathogenic potential of NIH444 to those of WM276, an Australian environmental isolate that is being used for the whole genome-sequencing project. Our data indicated that NIH444 is comparatively more virulent in a mouse model of cryptococcosis than is WM 276. We found robust mating of NIH444, and no mating of WM276, when tested against Cg MATa strain, NIH198. WM276 but not NIH444 was defective in filamentation and sporulation (haploid fruiting). Interestingly, NIH444 has a VGII/AFLP6 genotype similar to that of the genotype of the recent outbreak strains from Vancouver Island, British Columbia, Canada. Additionally, comparisons of nucleotide sequences of various genes also showed differences between NIH444 and WM276. Based on these observations, we conclude that NIH444 should remain the strain of choice for understanding Cg pathogenesis, especially on the North American continent.
Insights
Cryptococcus gattii strain NIH444 is more virulent and better suited for studying North American fungal infections than strain WM276. NIH444 exhibits robust mating and a genotype linked to recent outbreaks.
Area of Science:
- Mycology
- Infectious Diseases
- Molecular Pathogenesis
Background:
- Cryptococcus gattii (Cg) is an emerging fungal pathogen causing central nervous system infections.
- Strain NIH444 is a North American isolate, while WM276 is an Australian environmental isolate.
- Understanding Cg pathogenesis is crucial for public health.
Purpose of the Study:
- To compare the biological characteristics and pathogenic potential of Cg strains NIH444 and WM276.
- To determine the suitability of NIH444 for molecular pathogenesis studies in North America.
Main Methods:
- Virulence assessment in a mouse model of cryptococcosis.
- Mating assays with Cg MATa strain NIH198.
- Evaluation of filamentation and sporulation (haploid fruiting).
- Genotyping (VGII/AFLP6) and comparative gene sequencing.
Main Results:
- NIH444 demonstrated higher virulence in the mouse model compared to WM276.
- NIH444 exhibited robust mating, whereas WM276 did not.
- WM276 was defective in filamentation and sporulation, unlike NIH444.
- NIH444 shares a genotype (VGII/AFLP6) with recent Canadian outbreak strains.
Conclusions:
- Strain NIH444 is more virulent and biologically relevant for studying North American Cg pathogenesis.
- NIH444's characteristics make it the preferred strain for ongoing research on this continent.
