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.

Highlights

  • According to the world health organization, malarial cases are expected to double in recent times due to the much global focus to fight the covid-19 pandemic [1]

  • After γ-irradiation to a dose of 80 Gy, cell survivals of a mutant strain were significantly increased to 7.7- and 23.8-fold by putrescine and spermidine, respectively. Taken together these results suggest the probability that polyamines play a powerful role in the protection of DNA or cell damage by radiation

  • This suggests that both polyamines and heat shock proteins are used by the parasite Plasmodium falciparum as a strategy to survive under unfavorable conditions when it enters the human host from the mosquito [38–45]

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Summary

Introduction

According to the world health organization, malarial cases are expected to double in recent times due to the much global focus to fight the covid-19 pandemic [1]. It is reported that the temperature in the mosquito vector is about 22°C, whereas in the human host the normal body temperature is 37°C, but when the malaria symptoms kick in, the temperature goes as high as 38°C and above [3–5] These sudden temperature changes do not affect the parasite viability. To measure the viability of Escherichia coli cells lacking polyamines, they were grown in the medium containing putrescine and spermidine They displayed increased survivability compared to polyaminedepleted medium at a dose of 60 and 40 J/m2. After γ-irradiation to a dose of 80 Gy, cell survivals of a mutant strain were significantly increased to 7.7- and 23.8-fold by putrescine and spermidine, respectively Taken together these results suggest the probability that polyamines play a powerful role in the protection of DNA or cell damage by radiation. Polyamines can play an essential role in cell growth and differentiation and are involved in the protection of cell structures [10]

A Double Line of Defense
The life cycle of plasmodium falciparum parasite
Heat shock proteins
The functional activities of Hsp70 in partnership with Hsp40
Biosynthesis of polyamines
Obligate parasites have many “talents” of survival
Current drugs are available in the market for malaria
Proposed drug candidate
Findings
Conclusion and future perspectives
Full Text
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