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Low Diversity Cryptococcus neoformans Variety grubii Multilocus Sequence Types from Thailand Are Consistent with an Ancestral African Origin

Simwami, SP; Khayhan, K; Henk, DA; Aanensen, DM; Boekhout, T; Hagen, F; Brouwer, AE; Harrison, TS; Donnelly, CA; Fisher, MC (2011) Low Diversity Cryptococcus neoformans Variety grubii Multilocus Sequence Types from Thailand Are Consistent with an Ancestral African Origin. PLOS PATHOGENS, 7 (4). e001343 (1)-e001343 (22). ISSN 1553-7366
SGUL Authors: Harrison, Thomas Stephen

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The global burden of HIV-associated cryptococcal meningitis is estimated at nearly one million cases per year, causing up to a third of all AIDS-related deaths. Molecular epidemiology constitutes the main methodology for understanding the factors underpinning the emergence of this understudied, yet increasingly important, group of pathogenic fungi. Cryptococcus species are notable in the degree that virulence differs amongst lineages, and highly-virulent emerging lineages are changing patterns of human disease both temporally and spatially. Cryptococcus neoformans variety grubii (Cng, serotype A) constitutes the most ubiquitous cause of cryptococcal meningitis worldwide, however patterns of molecular diversity are understudied across some regions experiencing significant burdens of disease. We compared 183 clinical and environmental isolates of Cng from one such region, Thailand, Southeast Asia, against a global MLST database of 77 Cng isolates. Population genetic analyses showed that Thailand isolates from 11 provinces were highly homogenous, consisting of the same genetic background (globally known as VNI) and exhibiting only ten nearly identical sequence types (STs), with three (STs 44, 45 and 46) dominating our sample. This population contains significantly less diversity when compared against the global population of Cng, specifically Africa. Genetic diversity in Cng was significantly subdivided at the continental level with nearly half (47%) of the global STs unique to a genetically diverse and recombining population in Botswana. These patterns of diversity, when combined with evidence from haplotypic networks and coalescent analyses of global populations, are highly suggestive of an expansion of the Cng VNI clade out of Africa, leading to a limited number of genotypes founding the Asian populations. Divergence time testing estimates the time to the most common ancestor between the African and Asian populations to be 6,920 years ago (95% HPD 122.96 - 27,177.76). Further high-density sampling of global Cng STs is now necessary to resolve the temporal sequence underlying the global emergence of this human pathogen.

Item Type: Article
Additional Information: Copyright: © 2011 Simwami et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: AIDS-Related Opportunistic Infections, Africa, Anti-Retroviral Agents, Antifungal Agents, Cryptococcus neoformans, DNA, Fungal, Drug Therapy, Combination, Genes, Mating Type, Fungal, Genetic Variation, Humans, Meningitis, Cryptococcal, Molecular Epidemiology, Molecular Sequence Data, Mycological Typing Techniques, Phylogeny, Sequence Analysis, DNA, Species Specificity, Thailand, Science & Technology, Life Sciences & Biomedicine, Microbiology, Parasitology, Virology, MICROBIOLOGY, PARASITOLOGY, VIROLOGY, MATING-TYPE, SEROTYPE-A, VAR. GRUBII, STATISTICAL PROPERTIES, EMMONSIELLA-CAPSULATA, COCCIDIOIDES-IMMITIS, DNA POLYMORPHISM, UNITED-STATES, PERFECT STATE, GATTII, 0605 Microbiology, 1107 Immunology, 1108 Medical Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: PLOS PATHOGENS
ISSN: 1553-7366
Related URLs:
28 April 2011Published
Web of Science ID: WOS:000289979900009
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