Ehrlichia chaffeensis exploits Host SUMOylation pathways to mediate effector-host interactions and promote intracellular survival

Paige Selvy Dunphy, Tian Luo, Jere McBride

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Ehrlichia chaffeensis is an obligately intracellular Gram-negative bacterium that selectively infects mononuclear phagocytes. We recently reported that E. chaffeensis utilizes a type 1 secretion (T1S) system to export tandem repeat protein (TRP) effectors and demonstrated that these effectors interact with a functionally diverse array of host proteins. By way of these interactions, TRP effectors modulate host cell functions; however, the molecular basis of these interactions and their roles in ehrlichial pathobiology are not well defined. In this study, we describe the first bacterial protein posttranslational modification (PTM) by the small ubiquitin-like modifier (SUMO). The E. chaffeensis T1S effector TRP120 is conjugated to SUMO at a carboxy-terminal canonical consensus SUMO conjugation motif in vitro and in human cells. In human cells, TRP120 was selectively conjugated with SUMO2/3 isoforms. Disruption of TRP120 SUMOylation perturbed interactions with known host proteins, through predicted SUMO interaction motif-dependent and -independent mechanisms. E. chaffeensis infection did not result in dramatic changes in the global host SUMOylated protein profile, but a robust colocalization of predominately SUMO1 with ehrlichial inclusions was observed. Inhibiting the SUMO pathway with a small-molecule inhibitor had a significant impact on E. chaffeensis replication and recruitment of the TRP120-interacting protein polycomb group ring finger protein 5 (PCGF5) to the inclusion, indicating that the SUMO pathway is critical for intracellular survival. This study reveals the novel exploitation of the SUMO pathway by Ehrlichia, which facilitates effector-eukaryote interactions necessary to usurp the host and create a permissive intracellular niche.

Original languageEnglish (US)
Pages (from-to)4154-4168
Number of pages15
JournalInfection and Immunity
Volume82
Issue number10
DOIs
StatePublished - 2014

Fingerprint

Ehrlichia chaffeensis
Sumoylation
Ubiquitin
Survival
Tandem Repeat Sequences
Proteins
Polycomb-Group Proteins
Ehrlichia
Protein Array Analysis
Critical Pathways
Bacterial Proteins
Post Translational Protein Processing
Phagocytes
Eukaryota
Gram-Negative Bacteria
Fingers
Protein Isoforms

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Ehrlichia chaffeensis exploits Host SUMOylation pathways to mediate effector-host interactions and promote intracellular survival. / Dunphy, Paige Selvy; Luo, Tian; McBride, Jere.

In: Infection and Immunity, Vol. 82, No. 10, 2014, p. 4154-4168.

Research output: Contribution to journalArticle

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