An Ehrlichia chaffeensis tandem repeat protein interacts with multiple host targets involved in cell signaling, transcriptional regulation, and vesicle trafficking

Abdul Wakeel, Jeeba A. Kuriakose, Jere McBride

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Ehrlichia chaffeensis is an obligately intracellular bacterium that exhibits tropism for mononuclear phagocytes forming cytoplasmic membrane-bound microcolonies called morulae. To survive and replicate within phagocytes, E. chaffeensis exploits the host cell by modulating a number of host cell processes, but the ehrlichial effector proteins involved are unknown. In this study, we determined that p47, a secreted, differentially expressed, tandem repeat (TR) protein, interacts with multiple host proteins associated with cell signaling, transcriptional regulation, and vesicle trafficking. Yeast two-hybrid analysis revealed that p47 interacts with polycomb group ring finger 5 (PCGF5) protein, Src protein tyrosine kinase FYN (FYN), protein tyrosine phosphatase non-receptor type 2 (PTPN2), and adenylate cyclase-associated protein 1 (CAP1). p47 interaction with these proteins was further confirmed by coimmunoprecipitation assays and colocalization in HeLa cells transfected with p47-green fluorescent fusion protein (AcGFP1-p47). Moreover, confocal microscopy demonstrated p47-expressing dense-cored (DC) ehrlichiae colocalized with PCGF5, FYN, PTPN2, and CAP1. An amino-terminally truncated form of p47 containing TRs interacted only with PCGF5 and not with FYN, PTPN2, and CAP1, indicating differences in p47 domains that are involved in these interactions. These results demonstrate that p47 is involved in a complex network of interactions involving numerous host cell proteins. Furthermore, this study provides a new insight into the molecular and functional distinction of DC ehrlichiae, as well as the effector proteins involved in facilitating ehrlichial survival in mononuclear phagocytes.

Original languageEnglish
Pages (from-to)1734-1745
Number of pages12
JournalInfection and Immunity
Volume77
Issue number5
DOIs
StatePublished - May 2009

Fingerprint

Ehrlichia chaffeensis
Tandem Repeat Sequences
Non-Receptor Type 2 Protein Tyrosine Phosphatase
Proteins
Phagocytes
Ehrlichia
Fingers
Morula
Tropism
src-Family Kinases
Green Fluorescent Proteins
HeLa Cells
Adenylyl Cyclases
Confocal Microscopy

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

An Ehrlichia chaffeensis tandem repeat protein interacts with multiple host targets involved in cell signaling, transcriptional regulation, and vesicle trafficking. / Wakeel, Abdul; Kuriakose, Jeeba A.; McBride, Jere.

In: Infection and Immunity, Vol. 77, No. 5, 05.2009, p. 1734-1745.

Research output: Contribution to journalArticle

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