Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.

Bibliographic Details
Main Author: Chevalier, Frédéric D.
Publication Date: 2016
Other Authors: Le Clec’h, Winka, Eng, Nina, Rugel, Anastasia R., Assis, Rafael Ramiro de, Oliveira, Guilherme Correa de, Holloway, Stephen P., Cao, Xiaohang, Hart, P. John, LoVerde, Philip T., Anderson, Timothy J.C.
Format: Article
Language: eng
Source: Repositório Institucional da FIOCRUZ (ARCA)
Download full: https://www.arca.fiocruz.br/handle/icict/16290
Summary: 2021-01-01
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spelling Chevalier, Frédéric D.Le Clec’h, WinkaEng, NinaRugel, Anastasia R.Assis, Rafael Ramiro deOliveira, Guilherme Correa deHolloway, Stephen P.Cao, XiaohangHart, P. JohnLoVerde, Philip T.Anderson, Timothy J.C.2016-10-18T18:53:40Z2016-10-18T18:53:40Z2016CHEVALIER, Frédéric D. et al. Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population. Int J Parasitol., vol 46, n. 7, p. 417-24, 20160020-7519https://www.arca.fiocruz.br/handle/icict/1629010.1016/j.ijpara.2016.03.006engElsevier LtdSchistosoma mansoniBiochemical assayLoss-of-functionOxamniquine resistanceSchistosoma mansoniSoft selective eventSulfotransferaseIndependent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2021-01-01Texas Biomedical Research Institute. Department of Genetics. San Antonio, TX, USATexas Biomedical Research Institute. Department of Genetics. San Antonio, TX, USATexas Biomedical Research Institute. Department of Genetics. San Antonio, TX, USAUniversity of Texas Health Science Center. Department of Biochemistry. San Antonio, TX, USA/University of Texas Health Science Center. Department of Pathology. San Antonio, TX, USAFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil/Vale Instituto de Technologia. Belém, PA, BrasilUniversity of Texas Health Science Center. Department of Biochemistry. San Antonio, TX, USA/University of Texas Health Science Center. Department of Pathology. San Antonio, TX, USAUniversity of Texas Health Science Center. Department of Biochemistry. San Antonio, TX, USA/University of Texas Health Science Center. Department of Pathology. San Antonio, TX, USAUniversity of Texas Health Science Center. Department of Biochemistry. San Antonio, TX, USA/University of Texas Health Science Center. Department of Pathology. San Antonio, TX, USA/South Texas Veterans Health Care System. Department of Veterans Affairs. San Antonio, TX, USAUniversity of Texas Health Science Center. Department of Biochemistry. San Antonio, TX, USA/University of Texas Health Science Center. Department of Pathology. San Antonio, TX, USATexas Biomedical Research Institute. Department of Genetics. San Antonio, TX, USAMolecular surveillance provides a powerful approach to monitoring the resistance status of parasite populations in the field and for understanding resistance evolution. Oxamniquine was used to treat Brazilian schistosomiasis patients (mid-1970s to mid-2000s) and several cases of parasite infections resistant to treatment were recorded. The gene underlying resistance (SmSULT-OR) encodes a sulfotransferase required for intracellular drug activation. Resistance has a recessive basis and occurs when both SmSULT-OR alleles encode for defective proteins. Here we examine SmSULT-OR sequence variation in a natural schistosome population in Brazil ∼40years after the first use of this drug. We sequenced SmSULT-OR from 189 individual miracidia (1-11 per patient) recovered from 49 patients, and tested proteins expressed from putative resistance alleles for their ability to activate oxamniquine. We found nine mutations (four non-synonymous single nucleotide polymorphisms, three non-coding single nucleotide polymorphisms and two indels). Both mutations (p.E142del and p.C35R) identified previously were recovered in this field population. We also found two additional mutations (a splice site variant and 1bp coding insertion) predicted to encode non-functional truncated proteins. Two additional substitutions (p.G206V, p.N215Y) tested had no impact on oxamniquine activation. Three results are of particular interest: (i) we recovered the p.E142del mutation from the field: this same deletion is responsible for resistance in an oxamniquine selected laboratory parasite population; (ii) frequencies of resistance alleles are extremely low (0.27-0.8%), perhaps due to fitness costs associated with carriage of these alleles; (iii) that four independent resistant alleles were found is consistent with the idea that multiple mutations can generate loss-of-function alleles.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.
title Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.
spellingShingle Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.
Chevalier, Frédéric D.
Schistosoma mansoni
Biochemical assay
Loss-of-function
Oxamniquine resistance
Schistosoma mansoni
Soft selective event
Sulfotransferase
title_short Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.
title_full Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.
title_fullStr Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.
title_full_unstemmed Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.
title_sort Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.
author Chevalier, Frédéric D.
author_facet Chevalier, Frédéric D.
Le Clec’h, Winka
Eng, Nina
Rugel, Anastasia R.
Assis, Rafael Ramiro de
Oliveira, Guilherme Correa de
Holloway, Stephen P.
Cao, Xiaohang
Hart, P. John
LoVerde, Philip T.
Anderson, Timothy J.C.
author_role author
author2 Le Clec’h, Winka
Eng, Nina
Rugel, Anastasia R.
Assis, Rafael Ramiro de
Oliveira, Guilherme Correa de
Holloway, Stephen P.
Cao, Xiaohang
Hart, P. John
LoVerde, Philip T.
Anderson, Timothy J.C.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Chevalier, Frédéric D.
Le Clec’h, Winka
Eng, Nina
Rugel, Anastasia R.
Assis, Rafael Ramiro de
Oliveira, Guilherme Correa de
Holloway, Stephen P.
Cao, Xiaohang
Hart, P. John
LoVerde, Philip T.
Anderson, Timothy J.C.
dc.subject.other.pt_BR.fl_str_mv Schistosoma mansoni
topic Schistosoma mansoni
Biochemical assay
Loss-of-function
Oxamniquine resistance
Schistosoma mansoni
Soft selective event
Sulfotransferase
dc.subject.en.pt_BR.fl_str_mv Biochemical assay
Loss-of-function
Oxamniquine resistance
Schistosoma mansoni
Soft selective event
Sulfotransferase
description 2021-01-01
publishDate 2016
dc.date.accessioned.fl_str_mv 2016-10-18T18:53:40Z
dc.date.available.fl_str_mv 2016-10-18T18:53:40Z
dc.date.issued.fl_str_mv 2016
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv CHEVALIER, Frédéric D. et al. Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population. Int J Parasitol., vol 46, n. 7, p. 417-24, 2016
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/16290
dc.identifier.issn.pt_BR.fl_str_mv 0020-7519
dc.identifier.doi.none.fl_str_mv 10.1016/j.ijpara.2016.03.006
identifier_str_mv CHEVALIER, Frédéric D. et al. Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population. Int J Parasitol., vol 46, n. 7, p. 417-24, 2016
0020-7519
10.1016/j.ijpara.2016.03.006
url https://www.arca.fiocruz.br/handle/icict/16290
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier Ltd
publisher.none.fl_str_mv Elsevier Ltd
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/16290/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/16290/2/ve_Chevalier_Fr%c3%a9d%c3%a9ric_Independent_CPqRR_2016.pdf
https://www.arca.fiocruz.br/bitstream/icict/16290/3/ve_Chevalier_Fr%c3%a9d%c3%a9ric_Independent_CPqRR_2016.pdf.txt
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bitstream.checksumAlgorithm.fl_str_mv MD5
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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