Chaperone expression profiles correlate with distinct physiological states of Plasmodium falciparum in malaria patients.
BACKGROUND
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. 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.


METHODS
Chaperone networks operational in the distinct physiological clusters in clinical malaria parasites were constructed using cytoscape by utilizing their clinical expression profiles.


RESULTS
Molecular 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.


CONCLUSIONS
In all, this study demonstrates an intimate involvement of parasite-encoded chaperones, PfHsp90 in particular, in defining pathogenesis of malaria.
Pallavi
Rani
R
Department of Biochemistry, Indian Institute of Science, Bangalore, 560012 Karnataka, India.
Acharya
Pragyan
P
Chandran
Syama
S
Daily
Johanna P
JP
Tatu
Utpal
U
D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D006019:Glycolysis / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000378:metabolism* / Q000469:parasitology; D008954:Models, Biological; D018832:Molecular Chaperones / Q000032:analysis / Q000378:metabolism*; D016571:Neural Networks, Computer; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D015854:Up-Regulation
D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones