Our aim is to investigate the role of E-4-hydroxy-3methyl-but-2-enyl-pyrophosphate (HMBPP) as putative feeding stimulant attractant in Toxoplasma infected-mice. Apicomplexan protozoa use the MEP pathway that includes HMBPP while eukaryotes use the mevalonate (MVA) pathway for isoprenoids. Since Toxoplasma infection contributes to disease conditions in two hosts, the balance between genetical and behavioural alteration will be investigated. Toxoplasma infected-mice will be analysed in a spatial and temporal transcriptome (High-density spatial transcriptomics arrays for in situ tissue profiling). Finally, the mice will be exposed to parasite blend (parasite volatile organic compounds [VOC]) and the effects on behaviour, and appetite will be followed.
1 Lafferty, K. D. & Shaw, J. C. Comparing mechanisms of host manipulation across host and parasite taxa. J Exp Biol 216, 56-66, doi:10.1242/jeb.073668 (2013).
2 Cator, L. J., Lynch, P. A., Read, A. F. & Thomas, M. B. Do malaria parasites manipulate mosquitoes? Trends in Parasitology 28, 466-470, doi:Doi 10.1016/J.Pt.2012.08.004 (2012).
3 Rohmer, M. The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants. Nat Prod Rep 16, 565-574 (1999).
4 Morita, C. T., Jin, C., Sarikonda, G. & Wang, H. Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. Immunol Rev 215, 59-76, doi:10.1111/j.1600-065X.2006.00479.x (2007).
5 Heuston, S. et al. HmgR, a key enzyme in the mevalonate pathway for isoprenoid biosynthesis, is essential for growth of Listeria monocytogenes EGDe. Microbiology 158, 1684-1693, doi:10.1099/mic.0.056069-0 (2012).
6 Cassera, M. B. et al. The methylerythritol phosphate pathway is functionally active in all intraerythrocytic stages of Plasmodium falciparum. J Biol Chem 279, 51749-51759, doi:10.1074/jbc.M408360200 (2004).
7 Jomaa, H. et al. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science 285, 1573-1576 (1999).
8 Emami, S. N. et al. A key malaria metabolite modulates vector blood seeking, feeding, and susceptibility to infection. Science, doi:10.1126/science.aah4563 (2017).