Last Updated: 19/06/2024

Essential protein kinases as antimicrobial drug targets – applying chemical genetics in plasmodium falciparum and streptococcus pneumoniae

Objectives

To identify the substrates of PfCDPK5 and to elucidate the calcium-dependent signaling cascade for P. falciparum egress.

Specific objective:

To establish the chemical genetic approach in Streptococcus pneumoniae in order to study the protein kinase StkP which is an important pneumococcal virulence factor and a promising target for development of novel antibacterial drugs.

Principal Institution

Karolinska Institute (KI), Sweden

Principal Investigators / Focal Persons

Karin Blomqvist

Rationale and Abstract

Human malaria is a leading cause of death and disease worldwide. Infection by Plasmodium falciparum, the parasite that causes the most severe malaria, results in the death of one million individuals each year.
Resistance to existing anti-malarial medications is an emerging hurdle to the effective treatment of malaria. Thus there is a great need for new effective therapies, especially against severe malaria. A novel and essential calcium-dependent kinase, PfCDPK5, which is required for parasite egress, was recently identified by my American sponsor.We will utilize chemical genetics, applying the “holed kinase/bumped ATP” system to study PfCDPK5 in P. falciparum. The technique makes it possible to target a specific kinase and determine the role of the individual enzyme and its signaling networks.

Date

Jan 2013 — Dec 2016

Total Project Funding

$419,562

Funding Details
Swedish Research Council (SRC), Sweden

Grant ID: 2013-00367_VR
SEK 3.15M
Country / Project Site(s)

Sweden
United States

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