Targeting an essential Plasmodium cold shock protein to block growth and transmission of malaria parasite
Ankita Behl,
Rumaisha Shoaib,
Fernando De Leon,
Geeta Kumari,
Monika Saini,
Evanka Madan,
Vikash Kumar,
Harshita Singh,
Jyoti Kumari,
Preeti Maurya,
Swati Garg,
Prakash Chandra Mishra,
Christoph Arenz,
Shailja Singh
Affiliations
Ankita Behl
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Rumaisha Shoaib
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India; Department of Biosciences, Jamia Millia Islamia, New Delhi, India
Fernando De Leon
Institute for Chemistry, Humboldt University, Berlin, Germany
Geeta Kumari
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Monika Saini
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India; Department of Life Sciences, Shiv Nadar University, Greater Noida, Uttar Pradesh, India
Evanka Madan
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Vikash Kumar
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Harshita Singh
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Jyoti Kumari
Department of Life Sciences, Shiv Nadar University, Greater Noida, Uttar Pradesh, India
Preeti Maurya
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Swati Garg
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Prakash Chandra Mishra
Department of Biotechnology, Guru Nanak Dev University, Amritsar, India
Christoph Arenz
Institute for Chemistry, Humboldt University, Berlin, Germany
Shailja Singh
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India; Corresponding author
Summary: 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.
