| Author | Neto, Rubens Lima do Monte | |
| Author | Laffitte, Marie-Claude N. | |
| Author | Leprohon, Philippe | |
| Author | Reis, Priscila | |
| Author | Frézard, Frédéric | |
| Author | Ouellette, Marc | |
| Access date | 2022-02-04T18:08:05Z | |
| Available date | 2022-02-04T18:08:05Z | |
| Document date | 2015 | |
| Citation | 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 | pt_BR |
| ISSN | 1935-2735 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/51032 | |
| Language | eng | pt_BR |
| Publisher | Public Library of Science | pt_BR |
| Rights | open access | pt_BR |
| Title | Intrachromosomal Amplification, Locus Deletion and Point Mutation in the Aquaglyceroporin AQP1 Gene in Antimony Resistant Leishmania (Viannia) guyanensis | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1371/journal.pntd.0003476 | |
| Abstract | Background 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 parasites | pt_BR |
| Affilliation | 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 | pt_BR |
| Affilliation | 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 | pt_BR |
| Affilliation | 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 | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | 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 | pt_BR |
