A mitogen-activated protein (MAP) kinase homologue of Leishmania mexicana is essential for parasite survival in the infected host

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Abstract

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, Deltalmsap1/2, for the secreted acid phosphatase (SAP) gene locus, comprising the two SAP genes separated by an intergenic region of approximately 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 Deltalmsap1/2 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.

Original languageEnglish
Pages (from-to)2619-2628
Number of pages10
JournalThe EMBO journal
Volume17
Issue number9
DOIs
Publication statusPublished - 1 May 1998

Keywords

  • acid phosphatase
  • amino acid sequence
  • animals
  • base sequence
  • calcium-calmodulin-dependent protein kinases
  • DNA primers
  • genes, protozoan
  • genetic complementation test
  • introns
  • Leishmania mexicana
  • Leishmaniasis, Cutaneous
  • life cycle stages
  • mice
  • mice, inbred BALB C
  • molecular sequence data
  • mutagenesis, site-directed
  • open reading frames
  • polymerase chain reaction
  • protozoan proteins
  • rats
  • restriction mapping
  • sequence alignment
  • sequence deletion
  • sequence homology, amino acid

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