Anagu, LO, Hulse, DR, Horrocks, PD and Chakravorty, SJ (2022) Alteration of the expression of sirtuins and var genes by heat shock in the malaria parasite Plasmodium falciparum. Molecular and Biochemical Parasitology, 248. 111458 - 111458. ISSN 0166-6851

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Alteration of the expression of sirtuins and var genes by heat shock in the malaria parasite Plasmodium falciparum _ Elsevier Enhanced Reader.pdf - Accepted Version
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Abstract

Background
In Plasmodium falciparum the monoallelic expression of var virulence genes is regulated through epigenetic mechanisms. A study in the Gambia showed that an increase in var gene expression is associated with fever, high blood lactate with commonly-expressed var genes expressed in patients with severe malaria. A strong association was demonstrated between the upregulation of PfSir2A and group B var genes. A subsequent study in Kenya extended this association to show a link between elevated expression of PfSir2A and overall var transcript levels. We investigate here the link between heat shock and/or lactate levels on sirtuin and var gene expression levels in vitro.

Methods
In vitro experiments were conducted using laboratory and recently-laboratory-adapted Kenyan isolates of P. falciparum. To investigate a potential cause-and-effect relationship between host stress factors and parasite gene expression, qPCR was used to measure the expression of sirtuins and var genes after highly synchronous cultured parasites had been exposed to 2 h or 6 h of heat shock at 40 °C or elevated lactate.

Results
Heat shock was shown to increase the expression ofPfSir2B in the trophozoites, whereas exposure to lactate was not. After the ring stages were exposed to heat shock and lactate, there was no alteration in the expression of sirtuins and severe-disease-associated upsA and upsB var genes. The association between high blood lactate and sirtuin/var gene expression that was previously observed in vivo appears to be coincidental rather than causative.

Conclusions
This study demonstrates that heat stress in a laboratory and recently-laboratory-adapted isolates of P. falciparum results in a small increase in PfSir2B transcripts in the trophozoite stages only. This finding adds to our understanding of how patient factors can influence the outcome of Plasmodium falciparum infections.

Item Type: Article
Additional Information: The final version of this article and all relevant information related to it, including copyrights, can be found on the publisher website at; 10.1016/j.molbiopara.2022.111458
Uncontrolled Keywords: Plasmodium, var; Antigenic variation; Sirtuin; Sir2A; Sir2B; Heat shock
Subjects: R Medicine > R Medicine (General)
R Medicine > RA Public aspects of medicine
R Medicine > RB Pathology
Divisions: Faculty of Medicine and Health Sciences > School of Medicine
Faculty of Natural Sciences > School of Life Sciences
Depositing User: Symplectic
Date Deposited: 18 Jan 2022 15:43
Last Modified: 10 Jun 2022 08:45
URI: https://eprints.keele.ac.uk/id/eprint/10502

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