Effects of the disruption of the HSP70-II gene on the growth, morphology, and virulence of Leishmania infantum promastigotes.
Int Microbiol
; 11(2): 81-9, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18645958
ABSTRACT
The 70-kDa heat shock protein (HSP70) is highly conserved among both prokaryotes and eukaryotes and plays essential roles in diverse cellular functions not only under stress but also under normal conditions. In the protozoan Leishmania infantum, the causative agent of visceral leishmaniasis, HSP70 is encoded by two HSP70 genes. Here, we describe the phenotypic alterations of HSP70-II-deficient (Deltahsp70-II) promastigotes. The absence of HSP70-II caused a major alteration in growth as the promastigotes reached stationary phase. In addition, aberrant forms were frequently observed in Deltahsp70-II mutant cultures. An accumulation of cells in the G2/M phase in cultures of the Deltahsp70-II mutant was determined by flow cytometry. Furthermore, Deltahsp70-II promastigotes showed a limited capacity of multiplication within macrophages, even though attachment to and uptake by macrophages did not differ significantly from the wild-type. Moreover, Deltahsp70-II was highly attenuated in BALB/c mouse experimental infections. In mutants re-expressing HSP70-II, the growth rate was restored, the normal morphology was recovered, and interactions with macrophages increased. However, promastigotes re-expressing HSP70-II did not recover their virulence. Overall, these data highlight the essential role played by HSP70-II expression in Leishmania virulence, pointing to this gene as a promising target for therapeutic interventions.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deleção de Genes
/
Leishmania infantum
/
Proteínas de Choque Térmico HSP70
/
Leishmaniose Visceral
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Int Microbiol
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Espanha