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Infection and Immunity, October 2009, p. 4243-4255, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00376-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Nuclear Translocated Ehrlichia chaffeensis Ankyrin Protein Interacts with a Specific Adenine-Rich Motif of Host Promoter and Intronic Alu Elements {triangledown} ,{dagger}

Bing Zhu,1 Kimberly A. Nethery,1 Jeeba A. Kuriakose,1 Abdul Wakeel,1 Xiaofeng Zhang,1 and Jere W. McBride1,2,3,4,5*

Departments of Pathology,1 Microbiology and Immunology,2 Center for Biodefense and Emerging Infectious Diseases,3 Sealy Center for Vaccine Development,4 Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas 77555-06095

Received 2 April 2009/ Returned for modification 20 May 2009/ Accepted 28 July 2009

Ehrlichiae are obligately intracellular bacteria that reside and replicate in phagocytes by circumventing host cell defenses and modulating cellular processes, including host cell gene transcription. However, the mechanisms by which ehrlichiae influence host gene transcription have largely remained undetermined. Numerous ankyrin and tandem repeat-containing proteins associated with host-pathogen interactions have been identified in Ehrlichia species, but their roles in pathobiology are unknown. In this study, we determined by confocal immunofluorescence microscopy and by immunodetection in purified nuclear extracts that the ankyrin repeat-containing protein p200 is translocated to the nuclei of Ehrlichia-infected monocytes. Chromatin immunoprecipitation (ChIP) with DNA sequencing revealed an Ehrlichia chaffeensis p200 interaction located within host promoter and intronic Alu-Sx elements, the most abundant repetitive elements in the human genome. A specific adenine-rich (mid-A-stretch) motif within Alu-Sx elements was identified using electrophoretic mobility shift and NoShift assays. Whole-genome analysis with ChIP and DNA microarray analysis (ChIP-chip) determined that genes (n = 456) with promoter Alu elements primarily related to transcription, apoptosis, ATPase activity, and structural proteins associated with the nucleus and membrane-bound organelles were the primary targets of p200. Several p200 target genes (encoding tumor necrosis factor alpha, Stat1, and CD48) associated with ehrlichial pathobiology were strongly upregulated during infection, as determined by quantitative PCR. This is the first study to identify a nuclear translocation of bacterially encoded protein by E. chaffeensis and to identify a specific binding motif and genes that are primary targets of a novel molecular strategy to reprogram host cell gene expression to promote survival of the pathogen.

* Corresponding author. Mailing address: Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555-0609. Phone: (409) 747-2498. Fax: (409) 747-2455. E-mail: jemcbrid{at}utmb.edu

{triangledown} Published ahead of print on 3 August 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Camilli

Infection and Immunity, October 2009, p. 4243-4255, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00376-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Luo, T., Zhang, X., Nicholson, W. L., Zhu, B., McBride, J. W. (2010). Molecular Characterization of Antibody Epitopes of Ehrlichia chaffeensis Ankyrin Protein 200 and Tandem Repeat Protein 47 and Evaluation of Synthetic Immunodeterminants for Serodiagnosis of Human Monocytotropic Ehrlichiosis. CVI 17: 87-97 [Abstract] [Full Text]  


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