**2. The life cycle of** *plasmodium falciparum* **parasite**

The parasite *Plasmodium falciparum* has a complex life cycle which includes anopheles' female mosquito and the human host. After parasites have been sucked up, Oocysts develop in the gut wall of the mosquito. Sporozoites then develop in the oocyte and the Sporozoites migrate to the salivary glands. When the mosquito bites, Sporozoites are injected into the human body, who then becomes the second host to the parasites (**Figure 1**). The Sporozoites enter the liver cells where they multiply for about 7 to 14 days, producing between 10,000 and 30,000 daughter cells called merozoites. These daughter cells then burst and invade the red blood cells. In the red blood cells, further multiplication occurs by asexual reproduction [9, 10]. Between 8 and 16 merozoites are produced every 48 or 72 hours, depending on the species of *Plasmodium*. Merozoites are then released through the bursting of red blood cells. This release of toxic substances causes febrile attacks of the disease. After several such cycles, male and female gametocytes are produced (the sexual stage) and taken up by a feeding mosquito. The *Plasmodium* life cycle is completed by sexual reproduction, resulting in new sporozoites.

Some of the symptoms of malaria include but not all, fever and headache, these normally display when merozoite invade red blood cells and this stage is essential for the parasite survival. Fever is shown by elevated temperature above 38°C in the human host system. This therefore, puts stress on the cellular system of the parasite thus results in increased production of heat shock proteins for cellular system protection (protein folding). On the other hand, the parasite proliferates when the merozoite invades the red blood cells. The primary role of polyamines includes cell proliferation, differentiation, and growth of which are what the parasite needs at the red blood cell stage in a human host. Therefore, both heat shock proteins and polyamines serve as a shield of the parasite in the human host when exposed to stress conditions [17–20]. A study reported that the chaperone activities of Hsp70

#### **Figure 1.**

*Highlights of the* plasmodium falciparum *life cycle and the synthesis of heat shock proteins and polyamines under stressful conditions for the parasite survival. Female mosquito bites during the blood meal release sporozoites to liver cells, where they undergo maturation stage and rapture to release matured merozoites to invade red blood cells. At this stage, the parasite undergoes heat shock and release stress proteins such as a heat shock proteins and polyamines so that the parasite proliferates and grow.*

sequester protein aggregates accumulated in bacteria during antibiotic treatment, therefore reducing the effect of the cure. Also, polyamines such as putrescine and spermidine have been suggested to exhibit chaperone activities when cells are exposed to stressful environments such as antibiotic therapies [21]. Taken together, the role polyamines and heat shock proteins play in a cellular system suggests that *Plasmodium falciparum* could apply similar methods to render current drugs ineffective by keeping the system's proteins in good shape (properly folded) during drug treatment [22]. In general, obligate human parasites depend upon a robust protein quality control system to ensure their survival, and hence, both employ a competent heat shock machinery and polyamines to this end.

### **3. Heat shock proteins**

The outside milieu affects the in-house activity of the cellular system. If cells are exposed to stressful conditions, several molecular functions could be upset. For cells to remain functional active, the interior system should remain in good condition and if that is not the case, this could lead to cell death. Therefore, heat shock proteins of different sizes perform various functional activities to keep the cellular system in good condition. Molecular chaperone or heat shock proteins perform some activities as housekeepers of the cell, such as foldase, holdase, protein transportation, removal of inclusion bodies, modulation, and stabilization (**Table 1**). Whereas others are responsible for bringing the substrate for binding to reach a 3-dimensional structure. In *Plasmodium falciparum*, heat shock proteins have been regarded as ideal drug targets due to the aforementioned activities. Even though the role played by heat shock proteins favors the parasite viability, it is believed that their role in the parasite contributes to drug resistance. For example, when *E. coli* cells were exposed to some antibiotics, the production of Hsp70 chaperones was observed to have increased. It was then concluded that the cells developed resistance against antibiotics due to the

*A Double Line of Defense: Heat Shock Proteins and Polyamines Act as Contributing Factors… DOI: http://dx.doi.org/10.5772/intechopen.98852*


**Table 1.**

*Heat shock proteins and some compounds tested against them.*

increased production of Hsp70 [16]. *Plasmodium falciparum* parasite is believed to use the same techniques when exposed to various drugs by increasing the production of heat shock proteins as a strategy to protect its internal environment, thus developing resistance to many drugs available in the market [28, 29].

Different kinds of compounds have been synthesized and their effectiveness against heat shock proteins was tested [17]. The complex nature of the *P. falciparum* makes it very difficult to develop effective drugs or vaccines. It is therefore, this reason why drug design and development against malaria has drawn so much research interest as matter of urgency.
