Heat Shock Proteins of Malaria: What Do We Not Know, and What Should the Future Focus Be?

  • Addmore Shonhai
  • Gregory L. Blatch


As obligate parasites, malaria parasites have developed mechanisms for survival under unfavourable conditions in host cells. The chapters in this book have extensively discussed the evidence that heat shock proteins of malaria play a key role in parasite survival in host cells. The role of the heat shock protein arsenal of the parasite is not limited to the protection of the parasite cell, as some of these proteins also promote the pathological development of malaria. This is largely due to the export of a large number of these proteins to the infected erythrocyte cytosol. Although PfEMP1 is the main virulent factor for the malaria parasite, some of the exported malarial heat shock proteins appear to augment parasite virulence (Maier et al. 2008). While this book largely delves into experimentally validated information on the role of heat shock proteins in the development and pathogenicity of malaria, some of the information is is based on hypotheses yet to be fully tested. Therefore, it is important to highlight what we know to be definite roles of malarial heat shock proteins. This will help us distill information that could provide practical insights on the options available for future research directions, including interventions against malaria that may target the role of heat shock proteins in the development of the disease.


Heat Shock Protein Plasmodium Falciparum Plasmodium Falciparum Malaria Parasitophorous Vacuole Protein Quality Control 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Akide-Ndunge OB, Tambini E, Giribaldi G et al (2009) Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells. Malar J 8:113–127PubMedCrossRefGoogle Scholar
  2. Banumathy G, Singh V, Tatu U (2002) Host chaperones are recruited in membrane-BOUND complexes by Plasmodium falciparum. J Biol Chem 277:3902–3912PubMedCrossRefGoogle Scholar
  3. Banumathy G, Singh V, Pavithra SR et al (2003) Heat shock protein 90 is essential for Plasmodium falciparum growth in human erythrocytes. J Biol Chem 278:18336–18345PubMedCrossRefGoogle Scholar
  4. Chiang AN, Valderramos J-C, Balachandran R, et al (2009) Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum. Bioorg Med Chem 17:1527–1533Google Scholar
  5. Cockburn IL, Pesce ER, Pryzborski JM et al (2011) Screening for small molecule modulators of Hsp70 chaperone activity using protein aggregation suppression assays: inhibition of the plasmodial chaperone PfHsp70-1. Biol Chem 92:431–438Google Scholar
  6. de Koning-Ward TF, Gilson PR, Boddey JA et al (2009) A newly discovered protein export machine in malaria parasites. Nature 459:945–949PubMedCrossRefGoogle Scholar
  7. Edkins AL, Blatch GL (2012) Targeting conserved pathways as a strategy for novel drug development: disabling the cellular stress response. In: Chibale K (ed) Drug discovery in Africa. SpringerGoogle Scholar
  8. Grover M, Chaubey S, Ranade S, Tatu U (2013) Identification of an exported heat shock protein in Plasmodium falciparum. Parasite 20:2PubMedCrossRefGoogle Scholar
  9. Hiller NL, Bhattacharjee S, van Ooij C et al (2004) A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science 306:1934–1937PubMedCrossRefGoogle Scholar
  10. Külzer S, Rug M, Brinkmann K et al (2010) Parasite-encoded Hsp40 proteins define novel mobile structures in the cytosol of the P. falciparum-infected erythrocyte. Cell Microbiol 12:1398–1420PubMedCrossRefGoogle Scholar
  11. Külzer S, Charnaud S, Dagan T et al (2012) Plasmodium falciparum-encoded exported hsp70/hsp40 chaperone/co-chaperone complexes within the host erythrocyte. Cell Microbiol 14:1784–1795PubMedCrossRefGoogle Scholar
  12. Maier AG, Rug M, O’Neill M et al (2008) Exported proteins required for virulence and rigidity of Plasmodium falciparum infected human erythrocytes. Cell 134:48–61PubMedCrossRefGoogle Scholar
  13. Marti M, Good RT, Rug M et al (2004) Targeting malaria virulence and remodeling proteins to the host erythrocyte. Science 306:1930–1933PubMedCrossRefGoogle Scholar
  14. Morahan BJ, Strobel C, Hasan U et al (2011) Functional analysis of the exported Type IV HSP40 protein PfGECO in Plasmodium falciparum Gametocytes. Eukaryot Cell 10:1492–1503PubMedCrossRefGoogle Scholar
  15. Muralidharan V, Oksman A, Pal P et al (2012) Plasmodium falciparum heat shock protein 110 stabilizes the asparagine repeat-rich parasite proteome during malarial fevers. Nat Commun 3:1310. doi: 10.1038/ncomms2306PubMedCrossRefGoogle Scholar
  16. Njunge JM, Ludewig MH, Boshoff A et al (2013) Hsp70s and J proteins of Plasmodium parasites infecting rodents and primates: structure, function, clinical relevance, and drug targets. Curr Pharm Des 19:387–403PubMedCrossRefGoogle Scholar
  17. Nyalwidhe J, Lingelbach K (2006) Proteases and chaperones are the most abundant proteins in the parasitophorous vacuole of Plasmodium falciparum-infected erythrocytes. Proteomics 6:1563–1573PubMedCrossRefGoogle Scholar
  18. Pasini EM, Kirkegaard M, Mortensen P et al (2006) In-depth analysis of the membrane and cytosolic proteome of red blood cells. Blood 108:791–801PubMedCrossRefGoogle Scholar
  19. Pesce ER, Cockburn IL, Goble JL et al (2010) Malaria heat shock proteins: drug targets that chaperone other drug targets. Infect Disord Drug Targets 10:147–57PubMedCrossRefGoogle Scholar
  20. Shahinas D, MacMullin G, Benedict C, Crandall I, Pillai DR (2012) Harmine is a potent antimalarial targeting Hsp90 and synergizes with chloroquin and artemisinin. Antimicrob Agents Chemother 56:4207–4213PubMedCrossRefGoogle Scholar
  21. Shonhai A, Maier AG, Przyborski J et al (2011) Intracellular protozoan parasites of humans: The role of molecular chaperones in development and pathogenesis. Protein Peptide Lett 18:143–157Google Scholar
  22. Stephens LL, Shonhai A, Blatch GL (2011) The co-expression of the Plasmodium falciparum molecular chaperone, PfHsp70, increases the heterologous production of the potential drug target GTP cyclohydrolase I, PfGCHI. Protein Expr Purif 77:159–165CrossRefGoogle Scholar
  23. van Gestel RA, van Solinge WW, van der Toorn HW et al (2010) Quantitative erythrocyte membrane proteome analysis with Blue-native/SDS PAGE. J Proteomics 73:456–465PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of Biochemistry & MicrobiologyUniversity of ZululandKwaDlangezwaSouth Africa
  2. 2.College of Health and BiomedicineVictoria UniversityMelbourneAustralia

Personalised recommendations