Browsing by Autor "Louisa A. Messenger"

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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.
Development of Peptide-Based Lineage-Specific Serology for Chronic Chagas Disease: Geographical and Clinical Distribution of Epitope Recognition
(Public Library of Science, 2014) Tapan Bhattacharyya; Andrew K. Falconar; Alejandro O. Luquetti; Jaime A. Costales; Mario J. Grijalva; Michael D. Lewis; Louisa A. Messenger; Trang T. Tran; Juan David Ramírez; Felipe Guhl
These results demonstrate the considerable potential for synthetic peptide serology to investigate the infection history of individuals, geographical and clinical associations of T. cruzi lineages.
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.
Repeat-driven generation of antigenic diversity in a major human pathogen <i>Trypanosoma cruzi</i>
(2018) Carlos Talavera‐López; Louisa A. Messenger; Michael D. Lewis; Matthew Yeo; João Luís Reis-Cunha; Daniella Castanheira Bartholomeu; José E. Calzada; Azäel Saldaña; Juan David Ramírez; Felipe Guhl
ABSTRACT Trypanosoma cruzi , a zoonotic kinetoplastid protozoan with a complex genome, is the causative agent of American trypanosomiasis (Chagas disease). The parasite uses a highly diverse repertoire of surface molecules, with roles in cell invasion, immune evasion and pathogenesis. Thus far, the genomic regions containing these genes have been impossible to resolve and it has been impossible to study the structure and function of the several thousand repetitive genes encoding the surface molecules of the parasite. We here present an improved genome assembly of a T. cruzi clade I (TcI) strain using high coverage PacBio single molecule sequencing, together with Illumina sequencing of 34 T. cruzi TcI isolates and clones from different geographic locations, sample sources and clinical outcomes. Resolution of the surface molecule gene structure reveals an unusual duality in the organisation of the parasite genome, a core genomic region syntenous with related protozoa flanked by unique and highly plastic subtelomeric regions encoding surface antigens. The presence of abundant interspersed retrotransposons in the subtelomeres suggests that these elements are involved in a recombination mechanism for the generation of antigenic variation and evasion of the host immune response. The comparative genomic analysis of the cohort of TcI strains revealed multiple cases of such recombination events involving surface molecule genes and has provided new insights into T. cruzi population structure.