Publication Date:
2008-01-11
Description:
Calcium controls a number of critical events, including motility, secretion, cell invasion and egress by apicomplexan parasites. Compared to animal and plant cells, the molecular mechanisms that govern calcium signalling in parasites are poorly understood. Here we show that the production of the phytohormone abscisic acid (ABA) controls calcium signalling within the apicomplexan parasite Toxoplasma gondii, an opportunistic human pathogen. In plants, ABA controls a number of important events, including environmental stress responses, embryo development and seed dormancy. ABA induces production of the second-messenger cyclic ADP ribose (cADPR), which controls release of intracellular calcium stores in plants. cADPR also controls intracellular calcium release in the protozoan parasite T. gondii; however, previous studies have not revealed the molecular basis of this pathway. We found that addition of exogenous ABA induced formation of cADPR in T. gondii, stimulated calcium-dependent protein secretion, and induced parasite egress from the infected host cell in a density-dependent manner. Production of endogenous ABA within the parasite was confirmed by purification (using high-performance liquid chromatography) and analysis (by gas chromatography-mass spectrometry). Selective disruption of ABA synthesis by the inhibitor fluridone delayed egress and induced development of the slow-growing, dormant cyst stage of the parasite. Thus, ABA-mediated calcium signalling controls the decision between lytic and chronic stage growth, a developmental switch that is central in pathogenesis and transmission. The pathway for ABA production was probably acquired with an algal endosymbiont that was retained as a non-photosynthetic plastid known as the apicoplast. The plant-like nature of this pathway may be exploited therapeutically, as shown by the ability of a specific inhibitor of ABA synthesis to prevent toxoplasmosis in the mouse model.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877910/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nagamune, Kisaburo -- Hicks, Leslie M -- Fux, Blima -- Brossier, Fabien -- Chini, Eduardo N -- Sibley, L David -- R01 AI034036/AI/NIAID NIH HHS/ -- R01 AI034036-16/AI/NIAID NIH HHS/ -- R21 AI067051/AI/NIAID NIH HHS/ -- R21 AI067051-02/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Jan 10;451(7175):207-10. doi: 10.1038/nature06478.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18185591" target="_blank"〉PubMed〈/a〉
Keywords:
Abscisic Acid/analysis/biosynthesis/*metabolism/pharmacology
;
Animals
;
Calcium/*metabolism
;
*Calcium Signaling/drug effects
;
Cyclic ADP-Ribose/biosynthesis/metabolism
;
Disease Models, Animal
;
Mice
;
Mice, Inbred BALB C
;
Plant Growth Regulators
;
Protozoan Proteins/secretion
;
Pyridones/pharmacology
;
Toxoplasma/drug effects/*growth & development/*metabolism/pathogenicity
;
Toxoplasmosis/parasitology/pathology/prevention & control
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
