Deep sequencing of the trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital chagas disease patients

Llewellyn, M.S. et al. (2015) Deep sequencing of the trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital chagas disease patients. PLoS Neglected Tropical Diseases, 9(4), e0003458. (doi:10.1371/journal.pntd.0003458) (PMID:25849488) (PMCID:PMC4388557)

Llewellyn, M.S. et al. (2015) Deep sequencing of the trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital chagas disease patients. PLoS Neglected Tropical Diseases, 9(4), e0003458. (doi:10.1371/journal.pntd.0003458) (PMID:25849488) (PMCID:PMC4388557)

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Abstract

Background Chagas disease results from infection with the diploid protozoan parasite Trypanosoma cruzi. T. cruzi is highly genetically diverse, and multiclonal infections in individual hosts are common, but little studied. In this study, we explore T. cruzi infection multiclonality in the context of age, sex and clinical profile among a cohort of chronic patients, as well as paired congenital cases from Cochabamba, Bolivia and Goias, Brazil using amplicon deep sequencing technology. Methodology/ Principal Findings A 450bp fragment of the trypomastigote TcGP63I surface protease gene was amplified and sequenced across 70 chronic and 22 congenital cases on the Illumina MiSeq platform. In addition, a second, mitochondrial target—ND5—was sequenced across the same cohort of cases. Several million reads were generated, and sequencing read depths were normalized within patient cohorts (Goias chronic, n = 43, Goias congenital n = 2, Bolivia chronic, n = 27; Bolivia congenital, n = 20), Among chronic cases, analyses of variance indicated no clear correlation between intra-host sequence diversity and age, sex or symptoms, while principal coordinate analyses showed no clustering by symptoms between patients. Between congenital pairs, we found evidence for the transmission of multiple sequence types from mother to infant, as well as widespread instances of novel genotypes in infants. Finally, non-synonymous to synonymous (dn:ds) nucleotide substitution ratios among sequences of TcGP63Ia and TcGP63Ib subfamilies within each cohort provided powerful evidence of strong diversifying selection at this locus. Conclusions/Significance 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Llewellyn, Dr Martin
Authors: Llewellyn, M.S., Messenger, L.A., Luquetti, A.O., Garcia, L., Torrico, F., Tavares, S.B.N., Cheaib, B., Derome, N., Delepine, M., Baulard, C., Deleuze, J.-F., Sauer, S., and Miles, M.A.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2015 2015 Llewellyn et al.
First Published:First published in PLoS Neglected Tropical Diseases 9(4): e0003458
Publisher Policy:Reproduced under a Creative Commons License

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