A Double Line of Defense: Heat Shock Proteins and Polyamines Act as Contributing Factors to Drug Resistance of some Plasmodium Parasites

Abstract

Malaria remains a threat to human life worldwide with children under the age of 5 being the most vulnerable. Plasmodium falciparum, known as the causative agent of the deadliest malaria, survives both in the mosquito vector and human host. The sudden temperature change seems to not affect the parasite’s cellular system. Heat shock proteins and polyamines are the major house-keepers of the parasite’s cellular system to remain viable, despite the temperature changes that the parasite gets exposed to. While heat shock proteins protect newly synthesized proteins until they are properly folded polyamines are needed for cell differentiation, proliferation, and cell growth. In plants for example, polyamines have been reported to act as molecular chaperones when cells are exposed to unfavorable conditions that could be detrimental to cells. In this review, the role of heat shock proteins and polyamines in plasmodium parasite drug resistance and their role in parasite survival are discussed. The current drugs against malaria as well as the alternative future approach towards malarial drug development are reviewed.

The Computational Analysis ofPlasmodium falciparumHeat Shock Proteins Reveals an Interplay with Polyamines

“…The current treatment available in the market is not effective, due to the ever-changing parasite genome which then becomes resistant to the current drugs available in the market. This, therefore, needs urgent alternative treatment for malaria [24]. This study focused on three important polyamines namely: putrescine, spermidine, and spermine to establish the interaction with selected heat shock proteins.…”

Malaria therapeutics: are we close enough?

“…Role in RBC invasion [ 15 ] 45 Methionine aminopeptidase 1b Metalloproteases. Involved in protein maturation and activation by catalyzing the removal of the N-terminal initiator methionine during protein synthesis [ 77 ] 46 Mitogen-activated protein kinase 2 It plays a vital role in critical cellular processes and signal transduction [ 78 ] 47 N-myristoyl transferase The key enzyme of post-translational modifications [ 79 ] 48 NADH dehydrogenase type II It is an essential enzyme of the Plasmodium mitochondrial electron transport chain system [ 80 ] 49 Niemann-Pick Type C1 Present on the parasite’s plasma membrane—essential protein for the intraerythrocytic growth of Plasmodium falciparum [ 81 ] 50 Ornithine decarboxylase Involvement in polyamines biosynthesis (key component of transcription, translation, and several cellular processes) [ 82 ] 51 Orotatephospho-ribosyl transferase Crucial enzyme for the de novo pyrimidine synthesis pathway [ 83 ] 52 Orotidine 5′-monophosphate decarboxylase The key enzyme for the de novo pyrimidine synthesis pathway [ 84 ] 53 Orphan protein kinase PfPK7 An essential enzyme in the melatonin transduction pathway [ 85 ] 54 Pantothenic acid …”