Research by Nagamune et al. has revealed that the plant hormone abscisic acid (ABA) acts in the human parasite Toxoplasma gondii. In the protozoan parasite T. gondii, calcium release from intracellular stores (which has been implicated in various processes that involve calcium-mediated protein secretion) is regulated by the second messenger cyclic ADP ribose (cADPR). Noting that, in plants, ABA regulates calcium release from intracellular stores by means of cADPR, Nagamune et al. exposed T. gondii to ABA and found that it increased both their cADPR content and the calcium-dependent secretion of the adhesin MIC2 (microneme protein 2). Biochemical analyses indicated that ABA was present in T. gondii lysates, and enzyme-linked immunosorbent assay indicated that its concentration was decreased by treatment with the herbicide fluridone (which inhibits ABA synthesis in plants). There was a spike in the intracellular concentration of ABA before parasite egress from infected cells, and, whereas fluridone failed to prevent invasion of host cells, it inhibited T. gondii exit from infected human foreskin fibroblasts. Instead, it promoted differentiation of the parasites into tissue cysts. Exogenous ABA stimulated early egress of parasites from host cells and enabled egress in the presence of fluridone. Fluridone also decreased parasite burden in infected mice and markedly improved survival of mice inoculated with T. gondii. The authors thus conclude that a plantlike ABA-mediated calcium-signaling pathway is present in the protozoan T. gondii and that disruption of ABA signaling may provide a therapeutic approach against toxoplasmosis.
K. Nagamune, L. M. Hicks, B. Fux, F. Brossier, E. N. Chini, L. D. Sibley, Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii. Nature 451, 207-210 (2008). [PubMed]