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Sinclair SH, Garcia-Garcia JC, Dumler JS. Bioinformatic and mass spectrometry identification of Anaplasma phagocytophilum proteins translocated into host cell nuclei. Front Microbiol. 2015;6:55doi: 10.3389/fmicb.2015.00055.
Sinclair, S. H., Garcia-Garcia, J. C., & Dumler, J. S. (2015). Bioinformatic and mass spectrometry identification of Anaplasma phagocytophilum proteins translocated into host cell nuclei. Frontiers in microbiology, 655. https://doi.org/10.3389/fmicb.2015.00055
Sinclair, Sara H G, et al. "Bioinformatic and mass spectrometry identification of Anaplasma phagocytophilum proteins translocated into host cell nuclei." Frontiers in microbiology vol. 6 (2015): 55. doi: https://doi.org/10.3389/fmicb.2015.00055
Sinclair SH, Garcia-Garcia JC, Dumler JS. Bioinformatic and mass spectrometry identification of Anaplasma phagocytophilum proteins translocated into host cell nuclei. Front Microbiol. 2015 Feb 06;6:55. doi: 10.3389/fmicb.2015.00055. eCollection 2015. PMID: 25705208; PMCID: PMC4319465.
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Front Microbiol. 2015 Feb 06;6:55. doi: 10.3389/fmicb.2015.00055. eCollection 2015.

Bioinformatic and mass spectrometry identification of Anaplasma phagocytophilum proteins translocated into host cell nuclei.

Frontiers in microbiology

Sara H G Sinclair, Jose C Garcia-Garcia, J Stephen Dumler

Affiliations

  1. Graduate Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine Baltimore, MD, USA ; Department of Pathology, The Johns Hopkins University School of Medicine Baltimore, MD, USA ; Department of Pathology, University of Maryland School of Medicine Baltimore, MD, USA ; Department of Microbiology and Immunology, University of Maryland School of Medicine Baltimore, MD, USA.
  2. Department of Pathology, The Johns Hopkins University School of Medicine Baltimore, MD, USA ; Procter and Gamble Co. Cincinnati, OH, USA.

PMID: 25705208 PMCID: PMC4319465 DOI: 10.3389/fmicb.2015.00055

Abstract

Obligate intracellular bacteria have an arsenal of proteins that alter host cells to establish and maintain a hospitable environment for replication. Anaplasma phagocytophilum secrets Ankyrin A (AnkA), via a type IV secretion system, which translocates to the nucleus of its host cell, human neutrophils. A. phagocytophilum-infected neutrophils have dramatically altered phenotypes in part explained by AnkA-induced transcriptional alterations. However, it is unlikely that AnkA is the sole effector to account for infection-induced transcriptional changes. We developed a simple method combining bioinformatics and iTRAQ protein profiling to identify potential bacterial-derived nuclear-translocated proteins that could impact transcriptional programming in host cells. This approach identified 50 A. phagocytophilum candidate genes or proteins. The encoding genes were cloned to create GFP fusion protein-expressing clones that were transfected into HEK-293T cells. We confirmed nuclear translocation of six proteins: APH_0062, RplE, Hup, APH_0382, APH_0385, and APH_0455. Of the six, APH_0455 was identified as a type IV secretion substrate and is now under investigation as a potential nucleomodulin. Additionally, application of this approach to other intracellular bacteria such as Mycobacterium tuberculosis, Chlamydia trachomatis and other intracellular bacteria identified multiple candidate genes to be investigated.

Keywords: Anaplasma phagocytophilum; iTRAQ; nuclear translocation; nucleomodulin; oxidative burst

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