Analysis of the roles of cysteine proteinases of Leishmania mexicana in the host-parasite interaction.
Parasitology
; 121 ( Pt 4): 367-77, 2000 Oct.
Article
em En
| MEDLINE
| ID: mdl-11072899
ABSTRACT
Promastigotes of Leishmania mexicana mutants lacking the multicopy CPB cysteine proteinase genes (deltaCPB) are markedly less able than wild-type parasites to infect macrophages in vitro. deltaCPB promastigotes invade macrophages in large numbers but are unable to survive in the majority of the cells. In contrast, deltaCPB amastigotes invade and survive within macrophages in vitro. This extreme in vitro stage-specific difference was not mimicked in vivo; both promastigotes and amastigotes of deltaCPB produced lesions in BALB/c mice, but in each case the lesions grew considerably more slowly than those caused by wild-type parasites and only small lesions resulted. Inhibition of CPB in situ using cell-permeant peptidyl-diazomethylketones had no measurable effect on parasite growth or differentiation axenically in vitro. In contrast, N-benzoyloxycarbonyl-phe-ala-diazomethylketone reduced the infectivity of wild-type parasites to macrophages by 80%. Time-course experiments demonstrated that application of the inhibitor caused effects not seen with deltaCPB, suggesting that CPB may not be the prime target of this inhibitor. The data show that the CPB genes of L. mexicana encode enzymes that have important roles in intracellular survival of the parasite and more generally in its interaction with its mammalian host.
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Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Leishmania mexicana
/
Cisteína Endopeptidases
/
Interações Hospedeiro-Parasita
Limite:
Animals
País/Região como assunto:
Mexico
Idioma:
En
Revista:
Parasitology
Ano de publicação:
2000
Tipo de documento:
Article