Browsing by Autor "Martin Llewellyn"

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Candidate targets for Multilocus Sequence Typing of Trypanosoma cruzi: Validation using parasite stocks from the Chaco Region and a set of reference strains
(Elsevier BV, 2011) Juan José Lauthier; Nicolás Tomasini; Christian Barnabé; María M. Monje Rumi; Anahí M. Alberti D’Amato; Paula G. Ragone; Matthew Yeo; Michael D. Lewis; Martin Llewellyn; Miguel Á. Basombrío
Deep Sequencing of the Trypanosoma cruzi GP63 Surface Proteases Reveals Diversity and Diversifying Selection among Chronic and Congenital Chagas Disease Patients
(Public Library of Science, 2015) Martin Llewellyn; Louisa A. Messenger; Alejandro O. Luquetti; Lineth García; Faustino Torrico; Suelene B. N. Tavares; Bachar Cheaib; Nicolas Derôme; Marc Délepine; Céline Baulard
Our results shed light on the diversity of parasite DTUs within each patient, as well as the extent to which parasite strains pass between mother and foetus in congenital cases. Although we were unable to find any evidence that parasite diversity accumulates with age in our study cohorts, putative diversifying selection within members of the TcGP63I gene family suggests a link between genetic diversity within this gene family and survival in the mammalian host.
Ecological host fitting of <i><scp>T</scp>rypanosoma cruzi </i><scp>T</scp>c<scp>I</scp> in <scp>B</scp>olivia: mosaic population structure, hybridization and a role for humans in <scp>A</scp>ndean parasite dispersal
(Wiley, 2015) Louisa A. Messenger; Lineth García; Mathieu Vanhove; Carlos Huaranca; Marinely Bustamante; Mary‐Cruz Torrico; Faustino Torrico; Michael A. Miles; Martin Llewellyn
An improved understanding of how a parasite species exploits its genetic repertoire to colonize novel hosts and environmental niches is crucial to establish the epidemiological risk associated with emergent pathogenic genotypes. Trypanosoma cruzi, a genetically heterogeneous, multi-host zoonosis, provides an ideal system to examine the sylvatic diversification of parasitic protozoa. In Bolivia, T. cruzi I, the oldest and most widespread genetic lineage, is pervasive across a range of ecological clines. High-resolution nuclear (26 loci) and mitochondrial (10 loci) genotyping of 199 contemporaneous sylvatic TcI clones was undertaken to provide insights into the biogeographical basis of T. cruzi evolution. Three distinct sylvatic parasite transmission cycles were identified: one highland population among terrestrial rodent and triatomine species, composed of genetically homogenous strains (Ar = 2.95; PA/L = 0.61; DAS = 0.151), and two highly diverse, parasite assemblages circulating among predominantly arboreal mammals and vectors in the lowlands (Ar = 3.40 and 3.93; PA/L = 1.12 and 0.60; DAS = 0.425 and 0.311, respectively). Very limited gene flow between neighbouring terrestrial highland and arboreal lowland areas (distance ~220 km; FST = 0.42 and 0.35) but strong connectivity between ecologically similar but geographically disparate terrestrial highland ecotopes (distance >465 km; FST = 0.016-0.084) strongly supports ecological host fitting as the predominant mechanism of parasite diversification. Dissimilar heterozygosity estimates (excess in highlands, deficit in lowlands) and mitochondrial introgression among lowland strains may indicate fundamental differences in mating strategies between populations. Finally, accelerated parasite dissemination between densely populated, highland areas, compared to uninhabited lowland foci, likely reflects passive, long-range anthroponotic dispersal. The impact of humans on the risk of epizootic Chagas disease transmission in Bolivia is discussed.
Genome-Scale Multilocus Microsatellite Typing of Trypanosoma cruzi Discrete Typing Unit I Reveals Phylogeographic Structure and Specific Genotypes Linked to Human Infection
(Public Library of Science, 2009) Martin Llewellyn; Michael A. Miles; H. Carrasco; Michael D. Lewis; Matthew Yeo; Jorge Vargas; Faustino Torrico; Patricio Diosque; Vera Valente; Sebastião Aldo da Silva Valente
Trypanosoma cruzi is the most important parasitic infection in Latin America and is also genetically highly diverse, with at least six discrete typing units (DTUs) reported: Tc I, IIa, IIb, IIc, IId, and IIe. However, the current six-genotype classification is likely to be a poor reflection of the total genetic diversity present in this undeniably ancient parasite. To determine whether epidemiologically important information is "hidden" at the sub-DTU level, we developed a 48-marker panel of polymorphic microsatellite loci to investigate population structure among 135 samples from across the geographic distribution of TcI. This DTU is the major cause of resurgent human disease in northern South America but also occurs in silvatic triatomine vectors and mammalian reservoir hosts throughout the continent. Based on a total dataset of 12,329 alleles, we demonstrate that silvatic TcI populations are extraordinarily genetically diverse, show spatial structuring on a continental scale, and have undergone recent biogeographic expansion into the southern United States of America. Conversely, the majority of human strains sampled are restricted to two distinct groups characterised by a considerable reduction in genetic diversity with respect to isolates from silvatic sources. In Venezuela, most human isolates showed little identity with known local silvatic strains, despite frequent invasion of the domestic setting by infected adult vectors. Multilocus linkage indices indicate predominantly clonal parasite propagation among all populations. However, excess homozygosity among silvatic strains and raised heterozygosity among domestic populations suggest that some level of genetic recombination cannot be ruled out. The epidemiological significance of these findings is discussed.
Trypanosoma cruzi IIc: Phylogenetic and Phylogeographic Insights from Sequence and Microsatellite Analysis and Potential Impact on Emergent Chagas Disease
(Public Library of Science, 2009) Martin Llewellyn; Michael D. Lewis; Nidia Acosta; Matthew Yeo; H. Carrasco; Maikell Segovia; Jorge Vargas; Faustino Torrico; Michael A. Miles; Michael W. Gaunt
Trypanosoma cruzi, the etiological agent of Chagas disease, is highly genetically diverse. Numerous lines of evidence point to the existence of six stable genetic lineages or DTUs: TcI, TcIIa, TcIIb, TcIIc, TcIId, and TcIIe. Molecular dating suggests that T. cruzi is likely to have been an endemic infection of neotropical mammalian fauna for many millions of years. Here we have applied a panel of 49 polymorphic microsatellite markers developed from the online T. cruzi genome to document genetic diversity among 53 isolates belonging to TcIIc, a lineage so far recorded almost exclusively in silvatic transmission cycles but increasingly a potential source of human infection. These data are complemented by parallel analysis of sequence variation in a fragment of the glucose-6-phosphate isomerase gene. New isolates confirm that TcIIc is associated with terrestrial transmission cycles and armadillo reservoir hosts, and demonstrate that TcIIc is far more widespread than previously thought, with a distribution at least from Western Venezuela to the Argentine Chaco. We show that TcIIc is truly a discrete T. cruzi lineage, that it could have an ancient origin and that diversity occurs within the terrestrial niche independently of the host species. We also show that spatial structure among TcIIc isolates from its principal host, the armadillo Dasypus novemcinctus, is greater than that among TcI from Didelphis spp. opossums and link this observation to differences in ecology of their respective niches. Homozygosity in TcIIc populations and some linkage indices indicate the possibility of recombination but cannot yet be effectively discriminated from a high genome-wide frequency of gene conversion. Finally, we suggest that the derived TcIIc population genetic data have a vital role in determining the origin of the epidemiologically important hybrid lineages TcIId and TcIIe.