Image: Plasmodium falciparum (green) normally exports proteins (red) into its human erythrocyte host cells using the PTEX complex (upper left). Genetic attenuation of PTEX prevents export into the host cells leaving the exported proteins trapped around the parasite periphery (lower right).
Malaria kills more than half a million people in tropical countries every year where nearly half the world’s population live.
Malaria is caused by parasites that are spread from person to person by mosquito bite. The parasites infect and destroy our red blood cells, thereby making us very sick. The disease is particularly severe in young children and can even be fatal.
The potential of malaria parasites to do harm relies of their ability to modify their human host cells. By understanding how this happens we can develop new anti-malaria therapies.
Parasites have become resistant to many existing medicines so new ones have to be invented. The ability of parasites to grow quickly and to hide from our immune systems is due to their potential to renovate their host red blood cells by exporting effector proteins into them.
Recently we discovered molecular gateways called PTEX, that surround the parasites and help courier the exported proteins into their red blood cells. We found that when we stopped the parasites from making the PTEX gateways they rapidly died. We are now trying to develop new medicines that act like a plug to block the PTEX gateways thereby killing the parasites and curing the patient.
Publications
2014
- PTEX is an essential nexus for protein export in malaria parasites.
Elsworth B, Matthews K, Nie CQ, Kalanon M, Charnaud SC, Sanders PR, Chisholm SA, Counihan NA, Shaw PJ, Pino P, Chan J-A, Azevedo MF, Rogerson SJ, Beeson JG, Crabb BS, Gilson PR, de Koning-Ward TF
Nature. 2014 Jul; 511(7511):587-591
- Protein export in malaria parasites: an update.
Elsworth B, Crabb BS, Gilson PR
Cell Microbiol. 2014 Jan; 16(3):355-363
2013
- The Plasmodium translocon of exported proteins (PTEX) component thioredoxin-2 is important for maintaining normal blood-stage growth.
Matthews K, Kalanon M, Chisholm SA, Sturm A, Goodman CD, Dixon MW, Sanders PR, Nebl T, Fraser F, Haase S, McFadden GI, Gilson PR, Crabb BS, de Koning-Ward TF
Mol Microbiol. 2013 Jul; 89(6):1167-1186
- Spatial association with PTEX complexes defines regions for effector export into Plasmodium falciparum-infected erythrocytes.
Riglar DT, Rogers KL, Hanssen E, Turnbull L, Bullen HE, Charnaud SC, Przyborski J, Gilson PR, Whitchurch CB, Crabb BS, Baum J, Cowman AF
Nat Commun. 2013 Jan; 4:1415
2012
- Recent insights into the export of PEXEL/HTS-motif containing proteins in Plasmodium parasites.
Bullen HE, Crabb BS, Gilson PR
Curr Opin Microbiol. 2012 Oct; 152(6):699-704
- Plasmodium falciparum-encoded exported hsp70/hsp40 chaperone/co-chaperone complexes within the host erythrocyte.
Kulzer S, Charnaud S, Dagan T, Riedel J, Mandal P, Pesce ER, Blatch GL, Crabb BS, Gilson PR, Przyborski JM
Cell Microbiol. 2012 Aug; 14(11):1784-1795
- Biosynthesis, localisation and macromolecular arrangement of the Plasmodium falciparum translocon of exported proteins; PTEX.
Bullen HE, Charnaud SC, Kalanon M, Riglar DT, Dekiwadia C, Kangwanrangsan N, Torii M, Tsuboi T, Baum J, Ralph SA, Cowman AF, de Koning-Ward TF, Crabb BS, Gilson PR
J Biol Chem. 2012 Jan; 287(11):7871-7884
2010
- Protein export in Plasmodium parasites: from the endoplasmic reticulum to the vacuolar export machine.
Crabb BS, de Koning-Ward TF, Gilson PR
Int J Parasitol. 2010 Apr; 40(5):509-513
- An aspartyl protease directs malaria effector proteins to the host cell.
Boddey JA, Hodder AN, Günther S, Gilson PR, Patsiouras H, Kapp EA, Pearce JA, de Koning-Ward TF, Simpson RJ, Crabb BS, Cowman AF
Nature. 2010 Feb; 463(7281):627-631
2009
- A newly discovered protein export machine in malaria parasites.
de Koning-Ward TF, Gilson PR, Boddey JA, Rug M, Smith BJ, Papenfuss AT, Sanders PR, Lundie RJ, Maier AG, Cowman AF, Crabb BS
Nature. 2009 Jun; 459(7249):945-949