A Plasmodium falciparum histone deacetylase regulates antigenic variation and gametocyte conversion.

TitleA Plasmodium falciparum histone deacetylase regulates antigenic variation and gametocyte conversion.
Publication TypeJournal Article
Year of Publication2014
AuthorsColeman BI, Skillman KM, H Y Jiang R, Childs LM, Altenhofen LM, Ganter M, Leung Y, Goldowitz I, Kafsack BFC, Marti M, Llin√°s M, Buckee CO, Duraisingh MT
JournalCell Host Microbe
Volume16
Issue2
Pagination177-186
Date Published2014 Aug 13
ISSN1934-6069
KeywordsAmino Acid Sequence, Antigens, Protozoan, Cells, Cultured, Epigenesis, Genetic, Genes, Protozoan, Heterochromatin, Histone Deacetylases, Host-Parasite Interactions, Humans, Molecular Sequence Data, Plasmodium falciparum, Protozoan Proteins, Virulence
Abstract

The asexual forms of the malaria parasite Plasmodium falciparum are adapted for chronic persistence in human red blood cells, continuously evading host immunity using epigenetically regulated antigenic variation of virulence-associated genes. Parasite survival on a population level also requires differentiation into sexual forms, an obligatory step for further human transmission. We reveal that the essential nuclear gene, P. falciparum histone deacetylase 2 (PfHda2), is a global silencer of virulence gene expression and controls the frequency of switching from the asexual cycle to sexual development. PfHda2 depletion leads to dysregulated expression of both virulence-associated var genes and PfAP2-g, a transcription factor controlling sexual conversion, and is accompanied by increases in gametocytogenesis. Mathematical modeling further indicates that PfHda2 has likely evolved to optimize the parasite's infectious period by achieving low frequencies of virulence gene expression switching and sexual conversion. This common regulation of cellular transcriptional programs mechanistically links parasite transmissibility and virulence.

DOI10.1016/j.chom.2014.06.014
Alternate JournalCell Host Microbe
PubMed ID25121747
PubMed Central IDPMC4188636
Grant ListR21 AI105328 / AI / NIAID NIH HHS / United States
T32 HL007574 / HL / NHLBI NIH HHS / United States
P50GM071508 / GM / NIGMS NIH HHS / United States
R01 AI076276 / AI / NIAID NIH HHS / United States
P50 GM071508 / GM / NIGMS NIH HHS / United States
U54 GM088558 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
U54GM088558 / GM / NIGMS NIH HHS / United States
T32 5T32HL007574-31 / HL / NHLBI NIH HHS / United States

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