Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites

Author:

Clements Rebecca L.12ORCID,Morano Alexander A.12,Navarro Francesca M.12,McGee James P.23ORCID,Du Esrah W.2,Streva Vincent A.2,Lindner Scott E.3ORCID,Dvorin Jeffrey D.24ORCID

Affiliation:

1. Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115

2. Division of Infectious Diseases, Boston Children’s Hospital, Boston, MA 02115

3. Department of Biochemistry and Molecular Biology, the Huck Center for Malaria Research, Pennsylvania State University, University Park, PA 16802

4. Department of Pediatrics, Harvard Medical School, Boston, MA 02115

Abstract

Malaria remains a global driver of morbidity and mortality. To generate new antimalarials, one must elucidate the fundamental cell biology of Plasmodium falciparum , the parasite responsible for the deadliest cases of malaria. A membranous and proteinaceous scaffold called the inner membrane complex (IMC) supports the parasite during morphological changes, including segmentation of daughter cells during asexual replication and formation of transmission-stage gametocytes. The basal complex lines the edge of the IMC during segmentation and likely facilitates IMC expansion. It is unknown, however, what drives IMC expansion during gametocytogenesis. We describe the discovery of a basal complex protein, PfBLEB, which we find to be essential for gametocytogenesis. Parasites lacking PfBLEB harbor defects in IMC expansion and are unable to form mature gametocytes. This article demonstrates a role for a basal complex protein outside of asexual division, and, importantly, highlights a potential molecular target for the ablation of malaria transmission.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Reference49 articles.

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2. Malaria: Biology and Disease

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4. WHO, Global Report on Antimalarial Drug Efficacy and Drug Resistance: 2000–2010 (World Health Organization, Geneva, Switzerland, 2010).

5. The ABCs of multidrug resistance in malaria

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