Influence of calcium ion on host cell invasion and intracellular replication by Toxoplasma gondii

Abstract

Abstract:Toxoplasma gondii is an obligate intracellular protozoan parasite, which invades a wide range of hosts including humans. The exact mechanisms involved in its invasion are not fully understood. This study focused on the roles of Ca 2+ in host cell invasion and in T. gondii replication. We examined the invasion and replication of T. gondii pretreated with several calcium modulators, the conoid extrusion of tachyzoites. Calmodulin localization in T. gondii were observed using the immunogold method, and Ca 2+ levels in tachyzoites by confocal microscopy. In light microscopic observation, tachyzoites co-treated with A23187 and EGTA showed that host cell invasion and intracellular replication were decreased. The invasion of tachyzoites was slightly inhibited by the Ca 2+ channel blockers, bepridil and verapamil, and by the calmodulin antagonist, calmidazolium. We observed that calcium saline containing A23187 induced the extrusion of tachyzoite conoid. By immunoelectron microscopy, gold particles bound to anti-calmodulin or anti-actin mAb, were found to be localized on the anterior portion of tachyzoites. Remarkably reduced intracellular Ca 2+ was observed in tachyzoites treated with BAPTA/AM by confocal microscopy. These results suggest that host cell invasion and the intracellular replication of T. gondii tachyzoites are inhibited by the calcium ionophore, A23187, and by the extracellular calcium chelator, EGTA.

Toxoplasmosis and Polygenic Disease Susceptibility Genes: ExtensiveToxoplasma gondiiHost/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

“…TGF beta regulates proliferation, apoptosis, differentiation, and migration (definition from KEGG). Calcium channel blockers, calmodulin antagonism, or extracellular calcium depletion diminish cellular invasion by the parasite [69, 70]. The P53 and growth factor signalling networks (ErbB, VEGF) can be cancer related, while insulin signalling is evidently related to diabetes.…”

The Importance of Toxoplasma Gondii Infection in Diseases Presenting With Headaches. Headaches and Aseptic Meningitis May Be Manifestations of the Jarisch-Herxheimer Reaction

“…Calcium channel blockers, such as verapamil, bepridil, calmidazolium, and trifluoperazine, inhibited invasion of tachyzoites (Table 5). Thus, it is possible that antitoxoplasmal activity of valproic acid (VA), haloperidol, and other antipsychotic medications capable of inhibiting calcium transport through cellular ion channels, at least in part, was related to their calcium inhibitory properties (Carruthers & Sibley, 1999;Jones-Brando, Fuller Torrey, & Yolken, 2003;Pezzella et al, 1997;Song et al, 2004).…”

Induction and regulation of conoid extrusion inToxoplasma gondii

“…Conoid extrusion can be induced in extracellular tachyzoites by exposure to Ca 2+ ionophores (ionomycin and A23187) (Mondragón and Frixione, 1996;Monteiro et al, 2001), through a process regulated by the participation of intracellular Ca 2+ and actin filaments (Mondragón and Frixione, 1996); however, parasites suffer irreversible loss of their motility and invasive capability after the ionophore treatment followed by their death, probably due to an impairment of intracellular Ca 2+ regulation induced by these drugs (Mondragón and Frixione, 1996;Arrizabalaga and Boothroyd, 2004;Song et al, 2004).…”