How the malaria parasite defends itself from fever is unveiled
Study describes a gene that activates a protective response against high temperatures and other adverse conditions within the host

Date:
August 16, 2021
Source:
Barcelona Institute for Global Health (ISGlobal)
Summary:
A gene called PfAP2-HS allows the malaria parasite to defend itself
from adverse conditions in the host, including febrile temperatures,
according to new research. The study resolves a long-standing
question on how the parasite responds to changes in its environment.



FULL STORY ==========================================================================
A gene called PfAP2-HS allows the malaria parasite to defend itself
from adverse conditions in the host, including febrile temperatures,
according to a new study led by the Barcelona Institute for Global Health (ISGlobal), an institution supported by "la Caixa" Foundation. The study, published in Nature Microbiology, resolves a long-standing question on
how the parasite responds to changes in its environment.


========================================================================== Infection by Plasmodium falciparum, which causes one of the most severe
forms of malaria in humans, is characterised by periodic fevers (each
time a cycle of asexual reproduction is completed and parasites are
released into the blood stream). This is because fever is an important
element in our body's response against pathogens, since it affects the stability of cellular proteins and helps reduce parasite burden. In turn,
most organisms have a defence mechanism against increased temperatures:
the expression of heat-shock proteins (HSP), which act as chaperones.

"In most of the eukaryotic organisms, from yeasts to mammals, the
expression of these proteins depends on a highly conserved transcription
factor called HSF1," explains Alfred Corte's, ICREA researcher at ISGlobal
and study coordinator.

"However, malaria parasites -- which are also eukaryotes -- lack the HSF1
gene, although we know that they can survive at febrile temperatures,"
he adds.

In this study, Corte's and his team set out to investigate how the malaria parasite regulates its response to higher temperatures (or heat shock)
despite the absence of HSF1. They observed that a P. falciparum cell
line, grown in the laboratory, had lost its capacity to survive when
exposed to a temperature of 41.5-oC, and that this was due to a mutation
in a gene which they named PfAP2- HS. They showed that PfAP2-HS acts
as a transcription factor that activates the expression of heat shock
proteins hsp70-1 and hsp90 by binding to their respective promoters
(i.e. the "on-off button" of a gene). They also showed that engineered parasites lacking the PfAP2-HS gene not only had a lower survival when
exposed to higher temperatures, but also showed reduced growth at "normal" temperatures of 37-oC.

"This means that, in addition to its role in the protective heat-shock response, PfAP2-HS is also important for maintaining protein stability
in the parasite at basal temperatures," says Elisabet Tinto'-Font, first
author of the study. Moreover, absence of PfAP2-HS in P. falciparum
led to a higher susceptibility of the parasite to the antimalarial drug artemisinin, due to alterations in protein balance.

The research team found homologues of PfAP2-HS in all Plasmodium species analysed, even in those that infect mice and do not cause fever. "This
suggests that, at least in those species, the response orchestrated by
AP2-HS could protect against other adverse conditions in the host,"
says Corte's. "This is the first transcription factor described in
Plasmodium capable of regulating responses to adverse host conditions, including fever. PfAP2-HS acts as "an orchestra director," coordinating
the other proteins involved in the response," he adds.

========================================================================== Story Source: Materials provided by Barcelona_Institute_for_Global_Health_(ISGlobal). Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Elisabet Tinto'-Font, Lucas Michel-Todo', Timothy J. Russell, Nu'ria
Casas-Vila, David J. Conway, Zbynek Bozdech, Manuel Llina's,
Alfred Corte's. A heat-shock response regulated by the PfAP2-HS
transcription factor protects human malaria parasites from
febrile temperatures. Nature Microbiology, Aug. 16, 2021; DOI:
10.1038/s41564-021-00940-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210816112058.htm

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