Abstract
BackgroundMolecular chaperones have been shown to be important in the growth of the malaria parasite Plasmodium falciparum and inhibition of chaperone function by pharmacological agents has been shown to abrogate parasite growth. A recent study has demonstrated that clinical isolates of the parasite have distinct physiological states, one of which resembles environmental stress response showing up-regulation of specific molecular chaperones.MethodsChaperone networks operational in the distinct physiological clusters in clinical malaria parasites were constructed using cytoscape by utilizing their clinical expression profiles.ResultsMolecular chaperones show distinct profiles in the previously defined physiologically distinct states. Further, expression profiles of the chaperones from different cellular compartments correlate with specific patient clusters. While cluster 1 parasites, representing a starvation response, show up-regulation of organellar chaperones, cluster 2 parasites, which resemble active growth based on glycolysis, show up-regulation of cytoplasmic chaperones. Interestingly, cytoplasmic Hsp90 and its co-chaperones, previously implicated as drug targets in malaria, cluster in the same group. Detailed analysis of chaperone expression in the patient cluster 2 reveals up-regulation of the entire Hsp90-dependent pro-survival circuitries. In addition, cluster 2 also shows up-regulation of Plasmodium export element (PEXEL)-containing Hsp40s thought to have regulatory and host remodeling roles in the infected erythrocyte.ConclusionIn all, this study demonstrates an intimate involvement of parasite-encoded chaperones, PfHsp90 in particular, in defining pathogenesis of malaria.
Highlights
Molecular chaperones have been shown to be important in the growth of the malaria parasite Plasmodium falciparum and inhibition of chaperone function by pharmacological agents has been shown to abrogate parasite growth
Related heat shock proteins are co-expressed in the same group of patients Clinical isolates of P. falciparum have been reported to show distinct physiological states [7]
Cluster 3 has been sub-clustered with respect to Hsp90_C. This results in two subclusters; 3a and 3b, which differ in expression levels of cytosolic chaperones, indicating that cytosolic chaperones have distinct expression profiles in distinct physiological states and sub-states of the parasite
Summary
Molecular chaperones have been shown to be important in the growth of the malaria parasite Plasmodium falciparum and inhibition of chaperone function by pharmacological agents has been shown to abrogate parasite growth. The pathogen which encounters a change in pH, temperature, degrading enzymes and ROS, up-regulates its heat shock protein (Hsp) repertoire post infection. Previous studies suggest that the parasite relies on its repertoire of Hsps, PfHsp in particular, to establish and grow during heat shock [2]. These insights have been gleaned from studies on laboratory cultures of the parasite. The information that exists about the roles of parasite chaperones in infected patients is limited to the antigenic nature of parasite chaperone Hsp70-I
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
