Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/32933
Title: Growth arrested live-attenuated Leishmania infantum KHARON1 null mutants display cytokinesis defect and protective immunity in mice
Authors: Santi, Ana Maria Murta
Lanza, Juliane Sousa
Tunes, Luiza Guimarães
Fiuza, Jacqueline Araújo
Roy, Gaétan
Orfanó, Alessandra da Silva
Carvalho, Andréa Teixeira de
Frézard, Frédéric
Barros, André Luís Branco de
Murta, Silvane Maria Fonseca
Monte Neto, Rubens Lima do
Affilliation: Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Université Laval. Faculté de Médecine. Centre de Recherche en Infectiologie du Centre de Recherche du CHU de Québec et Département de Microbiologie, Infectiologie et Immunologie. Québec, Canada.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Abstract: There is no safe and efficacious vaccine against human leishmaniasis available and live attenuated vaccines have been used as a prophylactic alternative against the disease. In order to obtain an attenuated Leishmania parasite for vaccine purposes, we generated L. infantum KHARON1 (KH1) null mutants (Delta Likh1). This gene was previously associated with growth defects in L. mexicana. Delta Likh1 was obtained and confirmed by PCR, qPCR and Southern blot. We also generate a KH1 complemented line with the introduction of episomal copies of KH1. Although Delta Likh1 promastigote forms exhibited a growth pattern similar to the wild-type line, they differ in morphology without affecting parasite viability. L. infantum KH1-deficient amastigotes were unable to sustain experimental infection in macrophages, forming multinucleate cells which was confirmed by in vivo attenuation phenotype. The cell cycle analysis of Delta Likh1 amastigotes showed arrested cells at G(2)/M phase. Delta Likh1-immunized mice presented reduced parasite burden upon challenging with virulent L. infantum, when compared to naive mice. An effect associated with increased Li SLA-specific IgG serum levels and IL-17 production. Thus, Delta Likh1 parasites present an infective-attenuated phenotype due to a cytokinesis defect, whereas it induces immunity against visceral leishmaniasis in mouse model, being a candidate for antileishmanial vaccine purposes.
Keywords: leishmaniasis
L. infantum
keywords: Leishmanioses
L. infantum
Issue Date: 2018
Publisher: Nature Research
Citation: SANTI, Ana Maria Murta et al. Growth arrested live-attenuated Leishmania infantum KHARON1 null mutants display cytokinesis defect and protective immunity in mice. Scientific Reports, v. 8, art. 11627, 2018
DOI: 10.1038/s41598-018-30076-7
ISSN: 2045-2322
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos




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