A Plant-Like Kinase in Plasmodium falciparum Regulates Parasite Egress from Erythrocytes

Author:

Dvorin Jeffrey D.12,Martyn Derek C.3,Patel Saurabh D.14,Grimley Joshua S.5,Collins Christine R.6,Hopp Christine S.7,Bright A. Taylor8,Westenberger Scott8,Winzeler Elizabeth89,Blackman Michael J.6,Baker David A.7,Wandless Thomas J.5,Duraisingh Manoj T.1

Affiliation:

1. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

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

3. The Broad Institute, Cambridge, MA 02142, USA.

4. Division of Gastroenterology, Children’s Hospital Boston, Boston, MA 02115, USA.

5. Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.

6. Division of Parasitology, MRC National Institute for Medical Research, London NW7 1AA, UK.

7. London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.

8. Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

9. Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.

Abstract

It's a Knockout The malaria parasite is one of the most important pathogens of humans. Increasing drug-resistance is an imminent public health disaster, and we urgently need to find new drugs. The recently acquired malarial genomes provide a plethora of targets. However, due to the genetic intractability of the parasite, it has been difficult to identify essential genes in the clinically relevant blood-stage of the parasite. Dvorin et al. (p. 910 ) investigated the function of a Plasmodium falciparum plant-like calcium-dependent protein kinase, PfCDPK5, which is expressed in the invasive blood-stage forms of the parasite. A system for conditional protein expression allowed the production of a functional knockout in the bloodstream stage of the parasite. PfCDPK5 was required for parasite egress from the human host erythrocyte, an essential step in the parasite life cycle.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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