Use este identificador para citar ou linkar para este item:
https://www.arca.fiocruz.br/handle/icict/12786
Tipo de documento
ArtigoDireito Autoral
Acesso restrito
Coleções
Metadata
Mostrar registro completo
GENERATION OF AN AQUAGLYCEROPORIN AQP1 NULL MUTANT IN LEISHMANIA MAJOR
Aquaglyceroporin AQP1
Antimony resistance
Transport assays
Osmoregulation
Autor(es)
Afiliação
Faculté de Médecine. Université Laval. Centre de Recherche du CHU and Département de Microbiologie, Immunologie et Infectiologie. Centre de Recherche en Infectiologie. Québec, Québec, Canada.
Faculté de Médecine. Université Laval. Centre de Recherche du CHU and Département de Microbiologie, Immunologie et Infectiologie. Centre de Recherche en Infectiologie. Québec, Québec, Canada.
Herbert Wertheim College of Medicine. Molecular Microbiology and Infectious Diseases. Miami, USA.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil.
Herbert Wertheim College of Medicine. Molecular Microbiology and Infectious Diseases. Miami, USA.
Faculté de Médecine. Université Laval. Centre de Recherche du CHU and Département de Microbiologie, Immunologie et Infectiologie. Centre de Recherche en Infectiologie. Québec, Québec, Canada.
Faculté de Médecine. Université Laval. Centre de Recherche du CHU and Département de Microbiologie, Immunologie et Infectiologie. Centre de Recherche en Infectiologie. Québec, Québec, Canada.
Herbert Wertheim College of Medicine. Molecular Microbiology and Infectious Diseases. Miami, USA.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil.
Herbert Wertheim College of Medicine. Molecular Microbiology and Infectious Diseases. Miami, USA.
Faculté de Médecine. Université Laval. Centre de Recherche du CHU and Département de Microbiologie, Immunologie et Infectiologie. Centre de Recherche en Infectiologie. Québec, Québec, Canada.
Resumo em Inglês
The Leishmania aquaglyceroporin AQP1 plays an important physiological role in water and uncharged polar solutes transport, volume regulation, osmotaxis, and is a key determinant of antimony resistance. By targeted gene disruption, we generated a Leishmania major promastigote AQP1 null mutant. This required several attempts but a chromosomal null AQP1 mutant was obtained by loss of heterozygosity in the presence of a rescue plasmid encoding AQP1. Growth in the absence of selection led to the loss of the rescuing plasmid, indicating that AQP1 is not essential for Leishmania viability. The AQP1-null mutant was resistant to antimonyl tartrate (SbIII) and arsenite (AsIII) due to a decrease import of these metalloids. It also exhibited alterations in its osmoregulation abilities compared with wild-type cells. This is the first report of the generation of a genetic AQP1 null mutant in Leishmania parasite, confirming its physiological function and role in resistance to antimonials, the therapeutic mainstay against Leishmania.
Palavras-chave em inglês
LeishmaniaAquaglyceroporin AQP1
Antimony resistance
Transport assays
Osmoregulation
Compartilhar