Functional analysis of sirtuin genes in multiple Plasmodium falciparum strains

PloS One
Catherine J MerrickManoj T Duraisingh

Abstract

Plasmodium falciparum, the causative agent of severe human malaria, employs antigenic variation to avoid host immunity. Antigenic variation is achieved by transcriptional switching amongst polymorphic var genes, enforced by epigenetic modification of chromatin. The histone-modifying 'sirtuin' enzymes PfSir2a and PfSir2b have been implicated in this process. Disparate patterns of var expression have been reported in patient isolates as well as in cultured strains. We examined var expression in three commonly used laboratory strains (3D7, NF54 and FCR-3) in parallel. NF54 parasites express significantly lower levels of var genes compared to 3D7, despite the fact that 3D7 was originally a clone of the NF54 strain. To investigate whether this was linked to the expression of sirtuins, genetic disruption of both sirtuins was attempted in all three strains. No dramatic changes in var gene expression occurred in NF54 or FCR-3 following PfSir2b disruption, contrasting with previous observations in 3D7. In 3D7, complementation of the PfSir2a genetic disruption resulted in a significant decrease in previously-elevated var gene expression levels, but with the continued expression of multiple var genes. Finally, rearranged chromosomes were ...Continue Reading

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Citations

Jul 24, 2015·Nucleic Acids Research·Núria Rovira-GraellsAlfred Cortés
Apr 19, 2017·The Journal of Infectious Diseases·Sofía Mira-MartínezAlfred Cortés
Mar 23, 2017·Cold Spring Harbor Perspectives in Medicine·Alfred Cortés, Kirk W Deitsch
May 15, 2018·ChemMedChem·Mayibongwe J LungaClinton G L Veale
Jun 22, 2018·Annual Review of Microbiology·Manoj T Duraisingh, Kristen M Skillman
Jul 13, 2017·Annual Review of Microbiology·Kirk W Deitsch, Ron Dzikowski
Jul 14, 2017·Scientific Reports·Abhishek JamwalAmit Sharma
Jun 21, 2019·Briefings in Functional Genomics·Steven Abel, Karine G Le Roch
Nov 8, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Romain DuvalSylvie Michel
Jun 3, 2021·International Journal of Molecular Sciences·Maria Theresia WatzlowikGernot Längst

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Datasets Mentioned

BETA
GSE61940

Methods Mentioned

BETA
immunoprecipitation
electrophoresis
PCR
acetylation
histone acetylation

Software Mentioned

NimbleScan
Telometric

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