Cysteine peptidases CPA and CPB are vital for autophagy and differentiation in Leishmania mexicana

Roderick A Williams, Laurence Tetley, Jeremy C. Mottram, Graham H Coombs

Research output: Contribution to journalArticle

Abstract

In the past, ultrastructural investigations of Leishmania mexicana amastigotes revealed structures that were tentatively identified as autophagosomes. This study has now provided definitive data that autophagy occurs in the parasite during differentiation both to metacyclic promastigotes and to amastigotes, autophagosomes being particularly numerous during metacyclic to amastigote form transformation. Moreover, the results demonstrate that inhibiting two major lysosomal cysteine peptidases (CPA and CPB) or removing their genes not only interferes with the autophagy pathway but also prevents metacyclogenesis and transformation to amastigotes, thus adding support to the hypothesis that autophagy is required for cell differentiation. The study suggests that L. mexicana CPA and CPB perform similar roles to the aspartic peptidase PEP4 and the serine peptidase PRB1 in Saccharomyces cerevisiae. The results also provide an explanation for why L. mexicana CPA/CPB-deficient mutants transform to amastigotes very poorly and lack virulence in macrophages and mice.

Original languageEnglish
Pages (from-to)655-74
Number of pages20
JournalJournal of Medical Microbiology
Volume61
Issue number3
DOIs
Publication statusPublished - Aug 2006
Externally publishedYes

Fingerprint

Leishmania mexicana
Autophagy
Cysteine
Peptide Hydrolases
Serine
Virulence
Saccharomyces cerevisiae
Cell Differentiation
Parasites
Macrophages
Genes
Autophagosomes

Keywords

  • Animals
  • Animals, Genetically Modified
  • Autophagy
  • Cell Differentiation
  • Cells, Cultured
  • Cysteine Endopeptidases
  • Leishmania mexicana
  • Lysosomes
  • Macrolides
  • Macrophages, Peritoneal
  • Mice
  • Mice, Inbred Strains
  • Microtubules
  • Protozoan Proteins

Cite this

Williams, Roderick A ; Tetley, Laurence ; Mottram, Jeremy C. ; Coombs, Graham H. / Cysteine peptidases CPA and CPB are vital for autophagy and differentiation in Leishmania mexicana. In: Journal of Medical Microbiology. 2006 ; Vol. 61, No. 3. pp. 655-74.
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Cysteine peptidases CPA and CPB are vital for autophagy and differentiation in Leishmania mexicana. / Williams, Roderick A; Tetley, Laurence; Mottram, Jeremy C.; Coombs, Graham H.

In: Journal of Medical Microbiology, Vol. 61, No. 3, 08.2006, p. 655-74.

Research output: Contribution to journalArticle

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