Stress Response and Artemisinin Resistance in Malaria Parasite
[Technical Report, Annual Report]
Administrators of the Tulane Educational
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In malaria, drug resistance is a major treat to disease control efforts. Unfortunately, there is a significant knowledge gap in our understanding of the molecular mechanisms behind these phenomena. The current report provides an update in our efforts to explored the role of GRP78, a protein chaperone from the stress response, in arteminisin resistant parasites. The GRP78 expression at the mRNA and protein levels was evaluated in artemisinin sensitive and resistant Plasmodium falciparum strains. The results indicated a low base line GRP78 protein levels in the drug resistant parasites, and these levels did not increase significantly upon artemisinin exposure in any of the strains evaluated. A role for the chaperone in the recovery period after drug exposure will be investigated during the last period of this award. Additionally, P. falciparum GRP78 was expressed and purified from a heterologous system. The recombinant protein was used to characterize the binding of GRP78 inhibitors identified in the literature. The inhibitors were also evaluated in the growth inhibition activity against P. falciparum. This information identified inhibitors that preferentially affected PfGRP78, and the selected compounds will be used in the last period of the grant to evaluate the chaperone role upon artemsisin exposure.
- Medicine and Medical Research