16 research outputs found
Low diversity Cryptococcus neoformans variety grubii multilocus sequence types from Thailand are consistent with an ancestral African origin.
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The evolution of Cryptococcus neoformans var. grubii in the context of clinical disease using multilocus sequence typing
The global burden of HIV-associated cryptococcal meningitis (CM) is estimated
at one million cases per year, causing up to a third of all AIDS-related
deaths. Cryptococcus neoformans variety grubii (Cng) is the most
ubiquitous cause of cryptococcal meningitis worldwide, however patterns of
molecular diversity are understudied across some geographical regions experiencing
significant burdens of disease. 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. Molecular epidemiology constitutes the main methodology
for understanding the factors underpinning the emergence of this understudied,
yet increasingly important, group of pathogenic fungi. A multilocus
sequence typing (MLST) scheme was used to characterise a genetically
depauperate Cng population in Thailand, and a contrastingly highly diverse
Cng population in Cape Town, South Africa. Sequence types (STs)
from these populations were integrated into a dataset comprising global
STs of Cng and patterns of range expansion were traced. Evidence from
haplotypic networks and coalescent analyses revealed an ancestral African
population of molecular type VNB, from which emerged a VNI lineage. This
VNI lineage expanded globally out of Africa and led to the introduction of
a limited number of genotypes in novel regions, including Asia. Bayesian
inference estimated this spread of VNI to have occurred between 1 600 and
70 500 years ago, putatively vectored by the anthropogenically mediated
spread of domesticated pigeons, historically native African birds. Clinical
data collected from patients presenting with AIDS-associated CM showed
that infecting African Cng isolates were associated with poorer long-term
survival compared to Asian isolates. As mortality rates reported for these
patients in Sub-Saharan Africa are higher than those seen in Asia, supported
by a Galleria mellonella virulence model, this apparently elevated
virulence is postulated as being the result of recombinant progeny with diverse
phenotypes being created through frequent meiotic recombination
The evolution of Cryptococcus neoformans var. grubii in the context of clinical disease using multilocus sequence typing
The global burden of HIV-associated cryptococcal meningitis (CM) is estimated at one million cases per year, causing up to a third of all AIDS-related deaths. Cryptococcus neoformans variety grubii (Cng) is the most ubiquitous cause of cryptococcal meningitis worldwide, however patterns of molecular diversity are understudied across some geographical regions experiencing significant burdens of disease. 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. Molecular epidemiology constitutes the main methodology for understanding the factors underpinning the emergence of this understudied, yet increasingly important, group of pathogenic fungi. A multilocus sequence typing (MLST) scheme was used to characterise a genetically depauperate Cng population in Thailand, and a contrastingly highly diverse Cng population in Cape Town, South Africa. Sequence types (STs) from these populations were integrated into a dataset comprising global STs of Cng and patterns of range expansion were traced. Evidence from haplotypic networks and coalescent analyses revealed an ancestral African population of molecular type VNB, from which emerged a VNI lineage. This VNI lineage expanded globally out of Africa and led to the introduction of a limited number of genotypes in novel regions, including Asia. Bayesian inference estimated this spread of VNI to have occurred between 1 600 and 70 500 years ago, putatively vectored by the anthropogenically mediated spread of domesticated pigeons, historically native African birds. Clinical data collected from patients presenting with AIDS-associated CM showed that infecting African Cng isolates were associated with poorer long-term survival compared to Asian isolates. As mortality rates reported for these patients in Sub-Saharan Africa are higher than those seen in Asia, supported by a Galleria mellonella virulence model, this apparently elevated virulence is postulated as being the result of recombinant progeny with diverse phenotypes being created through frequent meiotic recombination.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Geographically structured populations of Cryptococcus neoformans Variety grubii in Asia correlate with HIV status and show a clonal population structure.
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125490.pdf (publisher's version ) (Open Access)Cryptococcosis is an important fungal disease in Asia with an estimated 140,000 new infections annually the majority of which occurs in patients suffering from HIV/AIDS. Cryptococcus neoformans variety grubii (serotype A) is the major causative agent of this disease. In the present study, multilocus sequence typing (MLST) using the ISHAM MLST consensus scheme for the C. neoformans/C. gattii species complex was used to analyse nucleotide polymorphisms among 476 isolates of this pathogen obtained from 8 Asian countries. Population genetic analysis showed that the Asian C. neoformans var. grubii population shows limited genetic diversity and demonstrates a largely clonal mode of reproduction when compared with the global MLST dataset. HIV-status, sequence types and geography were found to be confounded. However, a correlation between sequence types and isolates from HIV-negative patients was observed among the Asian isolates. Observations of high gene flow between the Middle Eastern and the Southeastern Asian populations suggest that immigrant workers in the Middle East were originally infected in Southeastern Asia
Analysis of Molecular Variance (AMOVA) of Asian <i>C</i>. <i>neoformans</i> according to HIV status and geographical origin.
<p>Analysis of Molecular Variance (AMOVA) of Asian <i>C</i>. <i>neoformans</i> according to HIV status and geographical origin.</p
Minimum spanning trees using the goeBURST algorithm showing MLST relationships among Asian C. neoformans var. <i>grubii</i> isolates.
<p>(A) Tree represents 476 <i>C</i>. <i>neoformans</i> var. <i>grubii</i> isolates from different countries. Each circle represents a unique genotype/sequence type (STs). The size of the circle corresponds to the number of isolates within that genotype. Different colors correspond to different countries; (B) Same as A, but now showing the genotypes from clinical and environmental sources; (C) Same as A and B, but with the addition of the genotypes of 179 <i>C</i>. <i>neoformans</i> var. <i>grubii</i> isolates from different continents (data from <a href="http://mlst.mycologylab.org" target="_blank">http://mlst.mycologylab.org</a> and previous reports by Cogliati <i>et al</i>., 2013 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072222#pone.0072222-Cogliati1" target="_blank">[44]</a> and Mihara <i>et al</i>., 2012 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072222#pone.0072222-Mihara1" target="_blank">[16]</a>).</p
Distribution of sequence types (STs) of <i>C</i>. <i>neoformans</i> var. <i>grubii</i> isolates according to HIV status of the patients.
<p>The predominant STs in each HIV status category are indicated in bold.</p
DNA polymorphisms in each MLST locus and concatenated sequences of Asian <i>C</i>. <i>neoformans</i> var. <i>grubii</i> isolates.
<p>S: number of polymorphic sites.</p><p>π: nucleotide diversity.</p><p>θ<sub>s</sub>: Watterson's θ per sequence.</p><p><i>k</i>: average number of nucleotide differences per sequence.</p><p>h: number of haplotypes.</p><p><i>H<sub>d</sub></i>: haplotype diversity.</p><p><i>D</i>, <i>F<sub>D</sub></i>, <i>F<sub>F</sub></i> and <i>F<sub>s</sub></i>: Tajima's D, Fu and Li's D*, Fu and Li's F* and Fu's Fs, respectively. The p value <0.05, *; <0.01, **; <0.001, ***.</p
Unrooted Neighbor-joining phylogenetic analysis of the concatenated MLST sequences found among Asian isolates.
<p>Numbers at each branch indicate bootstrap values >50%, based on 1,000 replicates. Each color rectangle represents the origin of isolates according to geographic origin, and clinical and environmental origin. Number inside each color rectangle indicates number of isolates.</p
Diagram showing DNA polymorphisms of <i>C.</i><i>neoformans</i> var. <i>grubii</i> from different Asian regions.
<p>(A) DNA polymorphism, genetic differentiation and gene flow; (B) same as A, but comparing African, American, Asian and European populations.</p