Ehrlichia chaffeensis TRP120 effector targets and recruits host polycomb group proteins for degradation to promote intracellular infection

Shubhajit Mitra, Paige S. Dunphy, Seema Das, Bing Zhu, Tian Luo, Jere McBride

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Ehrlichia chaffeensis has a group of well-characterized type I secreted tandem repeat protein (TRP) effectors that have moonlighting capabilities. TRPs modulate various cellular processes, reprogram host gene transcription as nucleomodulins, function as ubiquitin ligases, and directly activate conserved host cell signaling pathways to promote E. chaffeensis infection. One TRP-interacting host target is polycomb group ring finger protein 5 (PCGF5), a member of the polycomb group (PcG) protein family and a component of the polycomb repressive complex 1 (PRC1). The current study demonstrates that during early infection, PCGF5 strongly colocalizes with TRP120 in the nucleus and later dramatically redistributes to the ehrlichial vacuole along with other PCGF isoforms. Ectopic expression and immunoprecipitation of TRP120 confirmed the interaction of TRP120 with multiple different PCGF isoforms. At 48 h postinfection, a dramatic redistribution of PCGF isoforms from the nucleus to the ehrlichial vacuole was observed, which also temporally coincided with proteasomal degradation of PCGF isoforms and TRP120 expression on the vacuole. A decrease in PRC1-mediated repressive chromatin mark and an altered transcriptional activity in PRC1-associated Hox genes primarily from HOXB and HOXC clusters were observed along with the degradation of PCGF isoforms, suggesting disruption of the PRC1 in E. chaffeensis-infected cells. Notably, small interfering RNA (siRNA)-mediated knockdown of PCGF isoforms resulted in significantly increased E. chaffeensis infection. This study demonstrates a novel strategy in which E. chaffeensis manipulates PRC complexes through interactions between TRP120 and PCGF isoforms to promote infection.

Original languageEnglish (US)
Article numbere00845-17
JournalInfection and Immunity
Volume86
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Ehrlichia chaffeensis
Polycomb-Group Proteins
Polycomb Repressive Complex 1
Proteolysis
Protein Isoforms
Infection
Vacuoles
Tandem Repeat Sequences
Fingers
Proteins
Homeobox Genes
Ligases
Ubiquitin
Immunoprecipitation
Small Interfering RNA
Chromatin

Keywords

  • Ehrlichia chaffeensis
  • Hox gene
  • PCGF
  • Polycomb repressive complex
  • Tandem repeat protein

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Ehrlichia chaffeensis TRP120 effector targets and recruits host polycomb group proteins for degradation to promote intracellular infection. / Mitra, Shubhajit; Dunphy, Paige S.; Das, Seema; Zhu, Bing; Luo, Tian; McBride, Jere.

In: Infection and Immunity, Vol. 86, No. 4, e00845-17, 01.04.2018.

Research output: Contribution to journalArticle

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abstract = "Ehrlichia chaffeensis has a group of well-characterized type I secreted tandem repeat protein (TRP) effectors that have moonlighting capabilities. TRPs modulate various cellular processes, reprogram host gene transcription as nucleomodulins, function as ubiquitin ligases, and directly activate conserved host cell signaling pathways to promote E. chaffeensis infection. One TRP-interacting host target is polycomb group ring finger protein 5 (PCGF5), a member of the polycomb group (PcG) protein family and a component of the polycomb repressive complex 1 (PRC1). The current study demonstrates that during early infection, PCGF5 strongly colocalizes with TRP120 in the nucleus and later dramatically redistributes to the ehrlichial vacuole along with other PCGF isoforms. Ectopic expression and immunoprecipitation of TRP120 confirmed the interaction of TRP120 with multiple different PCGF isoforms. At 48 h postinfection, a dramatic redistribution of PCGF isoforms from the nucleus to the ehrlichial vacuole was observed, which also temporally coincided with proteasomal degradation of PCGF isoforms and TRP120 expression on the vacuole. A decrease in PRC1-mediated repressive chromatin mark and an altered transcriptional activity in PRC1-associated Hox genes primarily from HOXB and HOXC clusters were observed along with the degradation of PCGF isoforms, suggesting disruption of the PRC1 in E. chaffeensis-infected cells. Notably, small interfering RNA (siRNA)-mediated knockdown of PCGF isoforms resulted in significantly increased E. chaffeensis infection. This study demonstrates a novel strategy in which E. chaffeensis manipulates PRC complexes through interactions between TRP120 and PCGF isoforms to promote infection.",
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