Journal article

Lysine Acetylation in Sexual Stage Malaria Parasites Is a Target for Antimalarial Small Molecules

Katharine Trenholme, Linda Marek, Sandra Duffy, Gabriele Pradel, Gillian Fisher, Finn K Hansen, Tina S Skinner-Adams, Alice Butterworth, Che Julius Ngwa, Jonas Moecking, Christopher D Goodman, Geoffrey I McFadden, Subathdrage DM Sumanadasa, David P Fairlie, Vicky M Avery, Thomas Kurz, Katherine T Andrews

Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2014

Abstract

Therapies to prevent transmission of malaria parasites to the mosquito vector are a vital part of the global malaria elimination agenda. Primaquine is currently the only drug with such activity; however, its use is limited by side effects. The development of transmission-blocking strategies requires an understanding of sexual stage malaria parasite (gametocyte) biology and the identification of new drug leads. Lysine acetylation is an important posttranslational modification involved in regulating eukaryotic gene expression and other essential processes. Interfering with this process with histone deacetylase (HDAC) inhibitors is a validated strategy for cancer and other diseases, including a..

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Grants

Awarded by Australian Research Council


Awarded by Australian National Health and Medical Research Council


Awarded by Deutsche Forschungsgemeinschaft (DFG)


Funding Acknowledgements

This work was supported by the Australian Research Council (FT0991213 to K.T.A. and LP120200557 to V.M.A.), the Australian National Health and Medical Research Council (637406 to G.I.M., SPRF 1027369 to D.P.F., and NHMRC-EU 1074016 to K.T.A. and D.P.F.), and the Deutsche Forschungsgemeinschaft (DFG; PR905/7-1 to G.P.). Parts of this project were carried out as part of the A-PARADDISE program funded under the European Union's Seventh Framework Programme (FP7). C.J.N. received a fellowship from the Graduate School of Life Sciences of the University of Wurzburg. The DFG is acknowledged for funds used to purchase the UHR-TOF maXis 4G (Bruker Daltonics) Bremen HRMS instrument used in this research.