Leishmania species: Evidence for transglutaminase activity and its role in parasite proliferation

Reynolds K.B. Brobey, Lynn Soong

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Albeit transglutaminase (TGase) activity has been reported to play crucial physiological roles in several organisms including parasites; however, there was no previous report(s) whether Leishmania parasites exhibit this activity. We demonstrate herein that TGase is functionally active in Leishmania parasites by using labeled polyamine that becomes conjugated into protein substrates. The parasite enzyme was about 2- to 4-fold more abundant in Old World species than in New World ones. In L. amazonensis, comparable TGase activity was found in both promastigotes and amastigotes. TGase activity in either parasite stage was optimal at the basic pH, but the enzyme in amastigote lysates was more stable at higher temperatures (37-55 °C) than that in promastigote lysates. Leishmania TGase differs from mouse macrophage (MΦ) TGase in two ways: (1) the parasite enzyme is Ca2+-independent, whereas the mammalian TGase depends on the cation for activity, and (2) major protein substrates for L. amazonensis TGase were found within the 50-75 kDa region, while those for the MΦ TGase were located within 37-50 kDa. The potential contribution of TGase-catalyzed reactions in promastigote proliferation was supported by findings that standard inhibitors of TGase [e.g., monodansylcadaverine (MDC), cystamine (CS), and iodoacetamide (IodoA)], but not didansylcadaverine (DDC), a close analogue of MDC, had a profound dose-dependent inhibition on parasite growth. Myo-inositol-1-phosphate synthase and leishmanolysin (gp63) were identified as possible endogenous substrates for L. amazonensis TGase, implying a role for TGase in parasite growth, development, and survival.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalExperimental Parasitology
Volume114
Issue number2
DOIs
StatePublished - Oct 1 2006

Keywords

  • 2-[N-morpholino]ethanesulfonic acid
  • Amastigote
  • BCA
  • CS
  • DDC
  • FC
  • Glycoconjugates
  • Inhibition
  • IodoA
  • Leishmania
  • MDC
  • MES
  • PTM
  • Parasite
  • Promastigote
  • TGase
  • Transglutaminase (EC 2.3.2.13)
  • Trypanosomatid
  • Western blot
  • bicinchonic acid
  • cystamine
  • didansylcadaverine
  • fluorescein cadaverine
  • iodoacetamide
  • macrophage
  • monodansylcadaverine
  • posttranslational modification
  • transglutaminase

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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