Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients.
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...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0003458 https://doaj.org/article/68468006aa2e41d9bd0891943b94e677 |
id |
ftdoajarticles:oai:doaj.org/article:68468006aa2e41d9bd0891943b94e677 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:68468006aa2e41d9bd0891943b94e677 2023-05-15T15:16:40+02:00 Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients. Martin S Llewellyn Louisa A Messenger Alejandro O Luquetti Lineth Garcia Faustino Torrico Suelene B N Tavares Bachar Cheaib Nicolas Derome Marc Delepine Céline Baulard Jean-Francois Deleuze Sascha Sauer Michael A Miles 2015-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003458 https://doaj.org/article/68468006aa2e41d9bd0891943b94e677 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4388557?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003458 https://doaj.org/article/68468006aa2e41d9bd0891943b94e677 PLoS Neglected Tropical Diseases, Vol 9, Iss 4, p e0003458 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003458 2022-12-31T04:48:55Z 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 ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 4 e0003458 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Martin S Llewellyn Louisa A Messenger Alejandro O Luquetti Lineth Garcia Faustino Torrico Suelene B N Tavares Bachar Cheaib Nicolas Derome Marc Delepine Céline Baulard Jean-Francois Deleuze Sascha Sauer Michael A Miles Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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 ... |
format |
Article in Journal/Newspaper |
author |
Martin S Llewellyn Louisa A Messenger Alejandro O Luquetti Lineth Garcia Faustino Torrico Suelene B N Tavares Bachar Cheaib Nicolas Derome Marc Delepine Céline Baulard Jean-Francois Deleuze Sascha Sauer Michael A Miles |
author_facet |
Martin S Llewellyn Louisa A Messenger Alejandro O Luquetti Lineth Garcia Faustino Torrico Suelene B N Tavares Bachar Cheaib Nicolas Derome Marc Delepine Céline Baulard Jean-Francois Deleuze Sascha Sauer Michael A Miles |
author_sort |
Martin S Llewellyn |
title |
Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients. |
title_short |
Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients. |
title_full |
Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients. |
title_fullStr |
Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients. |
title_full_unstemmed |
Deep sequencing of the Trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients. |
title_sort |
deep sequencing of the trypanosoma cruzi gp63 surface proteases reveals diversity and diversifying selection among chronic and congenital chagas disease patients. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0003458 https://doaj.org/article/68468006aa2e41d9bd0891943b94e677 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 4, p e0003458 (2015) |
op_relation |
http://europepmc.org/articles/PMC4388557?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003458 https://doaj.org/article/68468006aa2e41d9bd0891943b94e677 |
op_doi |
https://doi.org/10.1371/journal.pntd.0003458 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
4 |
container_start_page |
e0003458 |
_version_ |
1766346971149238272 |