| Author | Santi, Ana Maria Murta | |
| Author | Lanza, Juliane Sousa | |
| Author | Tunes, Luiza Guimarães | |
| Author | Fiuza, Jacqueline Araújo | |
| Author | Roy, Gaétan | |
| Author | Orfanó, Alessandra da Silva | |
| Author | Carvalho, Andréa Teixeira de | |
| Author | Frézard, Frédéric | |
| Author | Barros, André Luís Branco de | |
| Author | Murta, Silvane Maria Fonseca | |
| Author | Monte Neto, Rubens Lima do | |
| Access date | 2019-05-03T13:29:40Z | |
| Available date | 2019-05-03T13:29:40Z | |
| Document date | 2018 | |
| 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 | pt_BR |
| ISSN | 2045-2322 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/32933 | |
| Language | eng | pt_BR |
| Publisher | Nature Research | pt_BR |
| Rights | restricted access | pt_BR |
| Subject in Portuguese | Leishmanioses | pt_BR |
| Subject in Portuguese | L. infantum | pt_BR |
| Title | Growth arrested live-attenuated Leishmania infantum KHARON1 null mutants display cytokinesis defect and protective immunity in mice | pt_BR |
| Type | Article | |
| DOI | 10.1038/s41598-018-30076-7 | |
| 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. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil. | pt_BR |
| Subject | leishmaniasis | pt_BR |
| Subject | L. infantum | pt_BR |
| Embargo date | 2025-01-01 | |
