Leishmania mexicana metacaspase is a negative regulator of amastigote proliferation in mammalian cells

E Castanys-Muñoz, E Brown, Graham Coombs, J C Mottram

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Metacaspases (MCAs) are caspase family cysteine peptidases that have been implicated in cell death processes in plants, fungi and protozoa. MCAs have also been suggested to be involved in cell cycle control, differentiation and clearance of aggregates; they are virulence factors. Dissecting the function of MCAs has been complicated by the presence in many organisms of multiple MCA genes or limitations on genetic manipulation. We describe here the creation of a MCA gene-deletion mutant (Δmca) in the protozoan parasite Leishmania mexicana, which has allowed us to dissect the role of the parasite's single MCA gene in cell growth and cell death. Δmca parasites are viable as promastigotes, and differentiate normally to the amastigote form both in in vitro macrophages infection and in mice. Δmca promastigotes respond to cell death inducers such as the drug miltefosine and H(2)O(2) similarly to wild-type (WT) promastigotes, suggesting that MCAs do not have a caspase-like role in execution of L. mexicana cell death. Δmca amastigotes replicated significantly faster than WT amastigotes in macrophages and in mice, but not as axenic culture in vitro. We propose that the Leishmania MCA acts as a negative regulator of amastigote proliferation, thereby acting to balance cell growth and cell death.
LanguageEnglish
Article numbere385
Number of pages9
JournalCell Death and Disease
Volume3
Early online date6 Sep 2012
DOIs
Publication statusPublished - 2012

Fingerprint

Leishmania mexicana
Cell Death
Parasites
miltefosine
Caspases
Macrophages
Axenic Culture
Leishmania
Gene Deletion
Virulence Factors
Growth
Cell Cycle Checkpoints
Genes
Cysteine
Peptide Hydrolases
Fungi
Infection
Pharmaceutical Preparations

Keywords

  • metacaspase
  • programmed cell death
  • cysteine peptidase
  • caspase
  • leishmania mexicana metacaspase
  • negative regulator
  • amastigote proliferation
  • mammalian cells

Cite this

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title = "Leishmania mexicana metacaspase is a negative regulator of amastigote proliferation in mammalian cells",
abstract = "Metacaspases (MCAs) are caspase family cysteine peptidases that have been implicated in cell death processes in plants, fungi and protozoa. MCAs have also been suggested to be involved in cell cycle control, differentiation and clearance of aggregates; they are virulence factors. Dissecting the function of MCAs has been complicated by the presence in many organisms of multiple MCA genes or limitations on genetic manipulation. We describe here the creation of a MCA gene-deletion mutant (Δmca) in the protozoan parasite Leishmania mexicana, which has allowed us to dissect the role of the parasite's single MCA gene in cell growth and cell death. Δmca parasites are viable as promastigotes, and differentiate normally to the amastigote form both in in vitro macrophages infection and in mice. Δmca promastigotes respond to cell death inducers such as the drug miltefosine and H(2)O(2) similarly to wild-type (WT) promastigotes, suggesting that MCAs do not have a caspase-like role in execution of L. mexicana cell death. Δmca amastigotes replicated significantly faster than WT amastigotes in macrophages and in mice, but not as axenic culture in vitro. We propose that the Leishmania MCA acts as a negative regulator of amastigote proliferation, thereby acting to balance cell growth and cell death.",
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Leishmania mexicana metacaspase is a negative regulator of amastigote proliferation in mammalian cells. / Castanys-Muñoz, E; Brown, E; Coombs, Graham; Mottram, J C.

In: Cell Death and Disease, Vol. 3, e385, 2012.

Research output: Contribution to journalArticle

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AU - Coombs, Graham

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