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A mitogen‐activated protein (MAP) kinase homologue of Leishmania mexicana is essential for parasite survival in the infected host
Author(s) -
Wiese Martin
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.9.2619
Subject(s) - biology , amastigote , leishmania , mutant , parasite hosting , gene , leishmania mexicana , protein kinase a , complementation , locus (genetics) , microbiology and biotechnology , genetics , kinase , world wide web , computer science
The parasitic protozoon Leishmania mexicana undergoes two major developmental stages in its life cycle exhibiting profound physiological and morphological differences, the promastigotes in the insect vector and the amastigotes in mammalian macrophages. A deletion mutant, Δ lmsap1/2 , for the secreted acid phosphatase (SAP) gene locus, comprising the two SAP genes separated by an intergenic region of ∼11.5 kb, lost its ability to cause a progressive disease in Balb/c mice. While in vitro growth of promastigotes, invasion of host cells and differentiation from promastigotes to amastigotes was indistinguishable from the wild‐type, the mutant parasites ceased to proliferate when transformed to amastigotes in infected macrophages or in a macrophage‐free in vitro differentiation system, suggesting a stage‐specific growth arrest. This phenotype could be reverted by complementation with 6 kb of the intergenic region of the SAP gene locus. Sequence analysis identified two open reading frames, both encoding single copy genes; one gene product shows high homology to mitogen‐activated protein (MAP) kinases. Complementation experiments revealed that the MAP kinase homologue, designated LMPK, is required and is sufficient to restore the infectivity of the Δ lmsap1/2 mutant. Therefore, LMPK is a kinase that is essential for the survival of L.mexicana in the infected host by affecting the cell division of the amastigotes.