Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis

Detalhes bibliográficos
Autor(a) principal: Neto, Rubens Lima do Monte
Data de Publicação: 2015
Outros Autores: Laffitte, Marie-Claude N., Leprohon, Philippe, Reis, Priscila, Frézard, Frédéric, Ouellette, Marc
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/51032
Resumo: Centre de Recherche en Infectiologie du Centre de Recherche du CHU Québec and Département de Microbiologie, Infectiologie et Immunologie. Faculté de Médecine. Université Laval. Québec, Québec, Canada/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brasil
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spelling Neto, Rubens Lima do MonteLaffitte, Marie-Claude N.Leprohon, PhilippeReis, PriscilaFrézard, FrédéricOuellette, Marc2022-02-04T18:08:05Z2022-02-04T18:08:05Z2015MONTE NETO, Rubens Lima et al. Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis. PLoS Negl Trop Dis., v. 9, n. 2, e0003476, 2015. doi: 10.1371/journal.pntd.00034761935-2735https://www.arca.fiocruz.br/handle/icict/5103210.1371/journal.pntd.0003476engPublic Library of ScienceIntrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCentre de Recherche en Infectiologie du Centre de Recherche du CHU Québec and Département de Microbiologie, Infectiologie et Immunologie. Faculté de Médecine. Université Laval. Québec, Québec, Canada/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, BrasilCentre de Recherche en Infectiologie du Centre de Recherche du CHU Québec and Département de Microbiologie, Infectiologie et Immunologie. Faculté de Médecine. Université Laval. Québec, Québec, CanadaCentre de Recherche en Infectiologie du Centre de Recherche du CHU Québec and Département de Microbiologie, Infectiologie et Immunologie. Faculté de Médecine. Université Laval. Québec, Québec, CanadaUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, BrasilCentre de Recherche en Infectiologie du Centre de Recherche du CHU Québec and Département de Microbiologie, Infectiologie et Immunologie. Faculté de Médecine. Université Laval. Québec, Québec, CanadaBackground Antimony resistance complicates the treatment of infections caused by the parasite Leishmania. Methodology/Principal Findings Using next generation sequencing, we sequenced the genome of four independent Leishmania guyanensis antimony-resistant (SbR) mutants and found different chromosomal alterations including aneuploidy, intrachromosomal gene amplification and gene deletion. A segment covering 30 genes on chromosome 19 was amplified intrachromosomally in three of the four mutants. The gene coding for the multidrug resistance associated protein A involved in antimony resistance was also amplified in the four mutants, most likely through chromosomal translocation. All mutants also displayed a reduced accumulation of antimony mainly due to genomic alterations at the level of the subtelomeric region of chromosome 31 harboring the gene coding for the aquaglyceroporin 1 (LgAQP1). Resistance involved the loss of LgAQP1 through subtelomeric deletions in three mutants. Interestingly, the fourth mutant harbored a single G133D point mutation in LgAQP1 whose role in resistance was functionality confirmed through drug sensitivity and antimony accumulation assays. In contrast to the Leishmania subspecies that resort to extrachromosomal amplification, the Viannia strains studied here used intrachromosomal amplification and locus deletion. Conclusions/Significance This is the first report of a naturally occurred point mutation in AQP1 in antimony resistant parasitesinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/51032/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALntrachromosomal Amplification, Locus Deletion and Point Mutation .pdfntrachromosomal Amplification, Locus Deletion and Point Mutation .pdfapplication/pdf7539829https://www.arca.fiocruz.br/bitstream/icict/51032/2/ntrachromosomal%20Amplification%2c%20Locus%20Deletion%20and%20Point%20Mutation%20.pdf42770030320dccad7ba32803ef40522cMD52icict/510322022-02-04 15:08:05.652oai:www.arca.fiocruz.br:icict/51032Tk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-02-04T18:08:05Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis
title Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis
spellingShingle Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis
Neto, Rubens Lima do Monte
title_short Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis
title_full Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis
title_fullStr Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis
title_full_unstemmed Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis
title_sort Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis
author Neto, Rubens Lima do Monte
author_facet Neto, Rubens Lima do Monte
Laffitte, Marie-Claude N.
Leprohon, Philippe
Reis, Priscila
Frézard, Frédéric
Ouellette, Marc
author_role author
author2 Laffitte, Marie-Claude N.
Leprohon, Philippe
Reis, Priscila
Frézard, Frédéric
Ouellette, Marc
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Neto, Rubens Lima do Monte
Laffitte, Marie-Claude N.
Leprohon, Philippe
Reis, Priscila
Frézard, Frédéric
Ouellette, Marc
description Centre de Recherche en Infectiologie du Centre de Recherche du CHU Québec and Département de Microbiologie, Infectiologie et Immunologie. Faculté de Médecine. Université Laval. Québec, Québec, Canada/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brasil
publishDate 2015
dc.date.issued.fl_str_mv 2015
dc.date.accessioned.fl_str_mv 2022-02-04T18:08:05Z
dc.date.available.fl_str_mv 2022-02-04T18:08:05Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv MONTE NETO, Rubens Lima et al. Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis. PLoS Negl Trop Dis., v. 9, n. 2, e0003476, 2015. doi: 10.1371/journal.pntd.0003476
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/51032
dc.identifier.issn.pt_BR.fl_str_mv 1935-2735
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pntd.0003476
identifier_str_mv MONTE NETO, Rubens Lima et al. Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis. PLoS Negl Trop Dis., v. 9, n. 2, e0003476, 2015. doi: 10.1371/journal.pntd.0003476
1935-2735
10.1371/journal.pntd.0003476
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dc.publisher.none.fl_str_mv Public Library of Science
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