Despite all efforts, malaria remains one of the deadliest diseases with an estimated 240.000.000 cases and more than 600.000 fatalities in 2020 alone. Sadly, most malaria deaths (60-75%) still occur in children aged under 5 years (World Malaria Report 2021). Thus, reducing the burden of malaria cases and deaths remains a global aim and medical challenge.
Like most eukaryotic cells, Plasmodium falciparum, the causative agent of malaria, relies on its cytoskeletal filaments, including microtubules, for proliferation, growth, and transmission. Indeed, microtubules and their molecular building block tubulin have gained outstanding importance as targets for drug development, in particular for a variety of cancers.
Despite the remarkable successes in chemotherapies, the development of parasite-specific tubulin drugs has been neglected. Although P. falciparum and human tubulin are very similar, molecular biologist and first author of the study William Hirst and colleagues reasoned that the tubulins were sufficiently divergent to identify compounds that would selectively disrupt parasite microtubules but would keep the human cytoskeleton intact.
Researchers can now screen for parasite-specific inhibitors
This research was funded by the Alliance Berlin-Canberra “Crossing Boundaries: Molecular Interactions in Malaria” which is co-funded by grants from the Deutsche Forschungsgemeinschaft (DFG) and the Australian National University (ANU) for the International Research Training Group (IRTG) 2290 at the IRI Life Sciences. It supported William Hirst and Dominik Fachet and enabled their stay in the lab of Kevin Saliba at the ANU, Canberra.
William G. Hirst, Dominik Fachet, Benno Kuropka, Christoph Weise, Kevin J. Saliba, Simone Reber. Purification of functional Plasmodium falciparum tubulin allows for the identification of parasite-specific microtubule inhibitors. Current Biology (2021). DOI: 10.1016/j.cub.2021.12.049
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