ORCID Profile
0000-0002-3390-8387
Current Organisation
University of Georgia
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Publisher: American Society for Microbiology
Date: 07-2013
DOI: 10.1128/IAI.00018-13
Abstract: Cryptococcus gattii is responsible for a large outbreak of potentially fatal disease that started in the late 1990s on Vancouver Island, Canada. How this fungus and the outbreak isolates in particular cause disease in immunocompetent people is unknown, with differing hypotheses. To explore genetic contributions, a pair of congenic a and α mating type strains was generated by a series of 11 backcrosses to introgress the MAT locus from a nonoutbreak strain into the background of strain R265, isolated from a Vancouver Island patient. The congenic pair was used to investigate three traits: mitochondrial inheritance, the effect of the MAT alleles on virulence, and the impact of a predicted virulence factor on pathogenicity. The two congenic strains show the same virulence in different models of cryptococcosis and equivalent levels of competition in coinfection assays. These results rule out a role of the MAT locus and mitochondrial genotype as major virulence factors in the outbreak strains. Disruption of Bwc2, a light-dependent transcription factor, resulted in reduced virulence, consistent with a similar function in the related species Cryptococcus neoformans . The C. gattii congenic strains represent a new resource for exploring the evolution of virulence in the C. neoformans-C. gattii clade.
Publisher: American Society for Microbiology
Date: 07-2013
DOI: 10.1128/IAI.00259-13
Abstract: Cryptococcus neoformans is an unconventional dimorphic fungus that can grow either as a yeast or in a filamentous form. To facilitate investigation of genetic factors important for its morphogenesis and pathogenicity, congenic a and α strains for a filamentous form were constructed. XL280 (α) was selected as the background strain because of its robust ability to undergo the morphological transition from yeast to the filamentous form. The MAT a allele from a sequenced strain JEC20 was introgressed into the XL280 background to generate the congenic a and α pair strains. The resulting congenic strains were then used to test the impact of mating type on virulence. In both the inhalation and the intravenous infection models of murine cryptococcosis, the congenic a and α strains displayed comparable levels of high virulence. The a -α coinfections displayed equivalent virulence to the in idual a or α infections in both animal models. Further analyses of the mating type distribution in a -α coinfected mice suggested no influence of a -α interactions on cryptococcal neurotropism, irrespective of the route of inoculation. Furthermore, deletion or overexpression of a known transcription factor, Znf2, in XL280 abolished or enhanced filamentation and biofilm formation, consistent with its established role. Overexpression of Znf2 in XL280 led to attenuation of virulence and a reduced abundance in the brain but not in other organs, suggesting that Znf2 might interfere with cryptococcal neurotropism upon extrapulmonary dissemination. In summary, the congenic strains provide a new resource for the exploration of the relationship in Cryptococcus between cellular morphology and pathogenesis.
Publisher: Springer Science and Business Media LLC
Date: 30-08-2005
DOI: 10.1038/NRMICRO1245
Abstract: Cryptococcus neoformans is a basidiomycete fungal pathogen of humans that has erged considerably from other model fungi such as Neurospora crassa, Aspergillus nidulans, Saccharomyces cerevisiae and the common human fungal pathogen Candida albicans. The recent completion of the genome sequences of two related C. neoformans strains and the ongoing genome sequencing of three other ergent Cryptococcus strains with different virulence phenotypes and environmental distributions should improve our understanding of this important pathogen. We discuss the biology of C. neoformans in light of this genomic data, with a special emphasis on the role that evolution and sexual reproduction have in the complex relationships of the fungus with the environment and the host.
Publisher: Elsevier BV
Date: 05-2015
Publisher: American Society for Microbiology
Date: 10-2008
DOI: 10.1128/EC.00097-08
Abstract: Sexual reproduction and genetic exchange are important for the evolution of fungal pathogens and for producing potentially infective spores. Studies to determine whether sex occurs in the pathogenic yeast Cryptococcus neoformans var . grubii have produced enigmatic results, however: basidiospores are the most likely infective propagules, and clinical isolates are fertile and genetically erse, consistent with a sexual species, but almost all populations examined consist of a single mating type and have little evidence for genetic recombination. The choice of population is critical when looking for recombination, particularly when significant asexual propagation is likely and when latency may complicate assessing the origin of an isolate. We therefore selected isolates from infected animals living in the region of Sydney, Australia, with the assumption that the relatively short life spans and limited travels of the animal hosts would provide a very defined population. All isolates were mating type α and were of molecular genotype VNI or VNII. A lack of linkage disequilibrium among loci suggested that genetic exchange occurred within both genotype groups. Four diploid VNII isolates that produced filaments and basidium-like structures when cultured in proximity to an a mating type strain were found. Recent studies suggest that compatible α-α unions can occur in C. neoformans var. neoformans populations and in populations of the sibling species Cryptococcus gattii . As a mating type strains of C. neoformans var. grubii have never been found in Australia, or in the VNII molecular type globally, the potential for α-α unions is evidence that α-α unisexual mating maintains sexual recombination and ersity in this pathogen and may produce infectious propagules.
Publisher: Oxford University Press (OUP)
Date: 03-04-2015
DOI: 10.1093/MMY/MYV012
Location: United States of America
No related grants have been discovered for Xiaorong Lin.