Targeting an essential Plasmodium cold shock protein to block growth and transmission of malaria parasite

• Published in: iScience 2023-05, Vol.26 (5), p.106637-106637, Article 106637
• Main Authors: Behl, Ankita, Shoaib, Rumaisha, De Leon, Fernando, Kumari, Geeta, Saini, Monika, Madan, Evanka, Kumar, Vikash, Singh, Harshita, Kumari, Jyoti, Maurya, Preeti, Garg, Swati, Chandra Mishra, Prakash, Arenz, Christoph, Singh, Shailja
• Format: Article
• Language: English
• Subjects: Biological sciences; Cell biology; Molecular biology; Parasitology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106637

Cold shock proteins are characterized by the presence of one or more cold shock domains that bestow them with nucleic acid binding ability. Although cold shock proteins are well characterized in bacteria, plants and humans, there is no information on their existence and role in malaria parasite. Here, we have identified and delineated the function of a cold shock protein of Plasmodium falciparum (Pf) ‘PfCoSP’. We demonstrate that PfCoSP exhibits nucleic acid binding properties and regulates gene expression. PfCoSP promotes microtubule assembly by interacting with Pf α/β tubulin. We identified a human cold shock protein LIN28A inhibitor ‘LI71’ as a binding partner of PfCoSP which inhibited PfCoSP–DNA and α/β tubulin interactions and, also inhibited the development of asexual blood stages and gametocyte stage of malaria parasite. Because PfCoSP is essential for parasite survival, characterization of its interacting partners may form the basis for development of future anti-malarials. [Display omitted] •PfCoSP exhibits nucleic acid binding properties and regulates gene expression•PfCoSP binds Pf α/β tubulin and promotes microtubule assembly•LI71 interacts with PfCoSP and inhibits its binding with DNA and tubulin•LI71 inhibits asexual and sexual development of malaria parasite Biological sciences; Molecular biology; Parasitology; Cell biology