Epigenetic silencing of host cell defense genes enhances intracellular survival of the rickettsial pathogen Anaplasma phagocytophilum

Jose C. Garcia-Garcia, Nicole C. Barat, Sarah J. Trembley, J. Stephen Dumler

Research output: Contribution to journalArticle

Abstract

Intracellular bacteria have evolved mechanisms that promote survival within hostile host environments, often resulting in functional dysregulation and disease. Using the Anaplasma phagocytophilum-infected granulocyte model, we establish a link between host chromatin modifications, defense gene transcription and intracellular bacterial infection. Infection of THP-1 cells with A. phagocytophilum led to silencing of host defense gene expression. Histone deacetylase 1 (HDAC1) expression, activity and binding to the defense gene promoters significantly increased during infection, which resulted in decreased histone H3 acetylation in infected cells. HDAC1 overexpression enhanced infection, whereas pharmacologic and siRNA HDAC1 inhibition significantly decreased bacterial load. HDAC2 does not seem to be involved, since HDAC2 silencing by siRNA had no effect on A. phagocytophilum intracellular propagation. These data indicate that HDAC up-regulation and epigenetic silencing of host cell defense genes is required for A. phagocytophilum infection. Bacterial epigenetic regulation of host cell gene transcription could be a general mechanism that enhances intracellular pathogen survival while altering cell function and promoting disease.

Original languageEnglish (US)
Article numbere1000488
JournalPLoS Pathogens
Volume5
Issue number6
DOIs
StatePublished - Jun 2009

Fingerprint

Anaplasma phagocytophilum
Epigenomics
Histone Deacetylase 1
Genes
Infection
Small Interfering RNA
Bacterial Load
Acetylation
Bacterial Infections
Granulocytes
Histones
Chromatin
Up-Regulation
Bacteria
Gene Expression

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Epigenetic silencing of host cell defense genes enhances intracellular survival of the rickettsial pathogen Anaplasma phagocytophilum. / Garcia-Garcia, Jose C.; Barat, Nicole C.; Trembley, Sarah J.; Dumler, J. Stephen.

In: PLoS Pathogens, Vol. 5, No. 6, e1000488, 06.2009.

Research output: Contribution to journalArticle

Garcia-Garcia, Jose C. ; Barat, Nicole C. ; Trembley, Sarah J. ; Dumler, J. Stephen. / Epigenetic silencing of host cell defense genes enhances intracellular survival of the rickettsial pathogen Anaplasma phagocytophilum. In: PLoS Pathogens. 2009 ; Vol. 5, No. 6.
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