E-4-hydroxy-3methyl-but-2-enyl pyrophosphate (HMBPP) is a precursor in the synthesis of isopentenyl pyrophosphate (IPP), the main building block for isoprenoids in nature. Apicomplexan protozoa and most bacteria use the methylene erythriol phosphate (MEP) pathway, including HMBPP, to synthesize IPP. Other eukaryotes, fungi, archaea and some bacteria use the mevalonate (MVA) pathway for IPP synthesis. Plants and a few bacteria use both the MEP and MVA pathways.
HMBPP is released as a malaria metabolite from all asexual and sexual stages of P. falciparum and confers 1) attraction of mosquitoes to malaria infected humans, 2) stimulating ingestion of larger blood meals, 3) increasing mosquito infectiousness with malaria and 4) regulating its antimalarial response proteins. Moreover, HMBPP is a well-studied 5) efficient activator of γδ T-lymphocyte proliferation in response to HMBPP released from Plasmodium falciparum and Mycobacteria tuberculosis (TBC) in the human host.
Since the balance between MEP/MVA bacteria in human microbiota and its release of HMBPP has not been studied before, the present aim is to investigate this. A distorted gut flora is known to contribute to several disease conditions like, obesity, anorexia, mental illness etc.Using MEP/MVA pathway inhibitors to treat feces from healthy humans, different samples of gut flora is achieved. The different bacterial contents are determined by an Illumina MiSeq system and HMBPP concentrations in corresponding culture media are estimated by mosquito feeding rate, or by γδ T cell proliferation. Germ free mice will be fed gavage with different MEP or MVA microbiota samples. The effects on their behavior, appetite and long term weight gain or loss will be recorded along with transcriptomics performed on brain, gut, liver and other tissues.

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Selected publications

Liu, Chenxiao; Emami, S. Noushin; Pettersson, Jean; Faye, Ingrid; Ranford–Cartwright, Lisa; Parmryd, Ingela.
V gamma 9V delta 2 T cells proliferate in response to phosphoantigens released from erythrocytes infected with asexual and gametocyte stage Plasmodium falciparum
Cellular Immunology, 2018 1090-2163, Vol. 334, s. 11-19

Emami, S. Noushin; Lindberg, Bo G.; Hua, Susanna; Hill, Sharon; Mozuraitis, Raimondas; Lehmann, Philipp; Birgersson, Göran; Borg-Karlson, Anna-Karin; Ignell, Rickard; Faye, Ingrid.  A key malaria metabolite modulates vector blood seeking, feeding, and susceptibility to infection. Science. 2017 Feb, DOI: 10.1126/science.aah4563

Kukutla. P.; Lindberg. BG.; Pei. D., Rayl. M.; Yu. W., Steritz. M.; Faye. I.; Xu. J. Insights from the genome annotation of Elizabethkingia anophelis from the malaria vector Anopheles gambiae. PLoS One. 2014 May 19;9(5)

Carter. V.; Underhill A.; Baber. I.; Sylla. L.; Baby. M.; Larget-Thiery. I.; Zettor. A.,; Bourgouin. C.; Langel. U.; Faye. I.; Otvos. L.; Wade. J.D.; Coulibaly. M.B.; Traore. SF.; Tripet. F.; Eggleston. P.; Hurd. H. Killer bee molecules: antimicrobial peptides as effector molecules to target sporogonic stages of Plasmodium. PLoS Pathog. 2013;9(11)

Kämpfer. P.; Matthews. H.; Glaeser. SP.; Martin. K., Lodders. N.; Faye. I. Elizabethkingia anophelis sp. nov., isolated from the midgut of the mosquito Anopheles gambiae. Int J Syst Evol Microbiol. 2011 Nov;61(Pt 11):2670-5. doi: 10.1099/ijs.0.026393-0. Epub 2010 Dec 17. Erratum in: Int J Syst Evol Microbiol. 2012 Apr;62(Pt 4):1016.

Lindberg. BG.; Merritt. EA.; Rayl. M, Liu. C.; Parmryd. I.; Olofsson. B.; Faye. I. Immunogenic and antioxidant effects of a pathogen-associated prenyl pyrophosphate in Anopheles gambiae. PLoS One. 2013 Aug 13;8(8)

Arrighi. R.B. and Faye. I. Plasmodium falciparum GPI toxin: a common foe for man and mosquito. Acta Trop. 2010 Jun;114(3):162-5.