Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population.
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/16290 |
Resumo: | 2021-01-01 |
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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 |
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2016-10-18T18:53:40Z |
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2016-10-18T18:53:40Z |
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2016 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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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 |
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https://www.arca.fiocruz.br/handle/icict/16290 |
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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 |
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Elsevier Ltd |
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Elsevier Ltd |
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