Plasmodium Falciparum Dubbed Most Deadly Malaria Parasite Regulates Its Reaction to High Fever, Here's How It Happens

A new study recently showed how a malaria parasite called Plasmodium Falciparum could defend itself and control its reactions to high fever, one of the main symptoms of malaria.

A Phys.org report specified that according to new research led by the Barcelona Institute for Global Health or ISGlobal, a la Caixa Foundation-supported institution, a gene identified as PfAP2-HS enables the malaria parasite to protect itself from negative conditions in the host, which include burning temperatures.

Essentially, this study resolves the long-lasting question of how the parasite reacts to changes within its environment.

'Plasmodium Falciparum'

An ISGlobal report said that infection by this particular malaria parasite, which causes one of the most severe malaria forms in humans, is characterized by episodic fevers every time a cycle of asexual reproduction is completed and parasites get released into the bloodstream.

This is because fever is an essential element of the body's response against pathogens since it impacts the cellular proteins' stability and helps reduce the parasite burden.

In turn, most organisms comprise a defense mechanism against high temperatures, the heat shock proteins or HSP's expression, acting as chaperones.

ICREA researcher Alfred Cortes, at ISGlobal and study coordinator, explained, in the majority of the eukaryotic organisms, from yeasts to mammals, these proteins' expression is reliant on a highly conserved transcription factor known as HSF1.

Nevertheless, he added, malaria parasites, which are also known as eukaryotes, don't have the HSF1 genes, even though it's known that they can survive at feverish or burning temperatures.

Regulating Its Response to High Fever

In the study, A heat-shock response regulated by the PfAP2-HS transcription factor protects human malaria parasites from febrile temperatures, published in Nature Microbiology, Cortes, together with his team, started to investigate the manner malaria parasite is regulating its reaction to heat shock or higher temperatures despite the lack of HSF1.

As a result, the researchers observed that a "P. falciparum cell line" grown in the lab had lost its ability to survive when exposed to a high 41.5-degree Celsius temperature and that this was because of a mutation in a gene they then labeled as PfAP2-HS.

The study investigators showed that PfAP2-HS acts as a transcription factor that stimulates the expression of "heat shock proteins hsp70-1 and hsp90" by tying to their respective promoters, for instance, the gene's on-off button.

In addition, the researchers showed too, the engineered parasites that lacked the PfAP2-HS gene not only comprised a lower survival when they got exposed to a higher temperature, but they showed a reduction in growth as well, at a normal 37-degree Celsius temperature.

The 'Orchestra Director

According to the study's first author Elisabet Tintó-Font, their findings mean that, in addition to its function in the protective heat-shock reaction, PfAP2-HS is essential too for the maintenance of protein stability in the parasite at basal temperatures.

Furthermore, the lack of PfAP2-HS in this said malaria parasite resulted in a higher vulnerability of the Plasmodium falciparum to the antimalarial drug artemisinin, described in the National Library of Medicine, an olden Chinese herbal treatment for malarial fevers, because of changes in protein balance.

The team discovered homologs of PfAP2-HS in all species of Plasmodium examined, even in those that infect rodents and do not result in fever.

Cortes explained, this then suggests that, at least in the said species, the reaction AP2-HS orchestrated could shield against other hostile conditions in the host.

He added that this is the first transcription factor defined in Plasmodium to regulate reactions to adverse host conditions, which includes fever.

Lastly, the study's first author elaborated that PfAP2-HS functions as an "orchestra director," coordinating the other proteins engaged in the response.

Related information about Malaria and Plasmodium Falciparum is shown on Nanolive's YouTube video below:

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