Anaplasma phagocytophilum AnkA binds to granulocyte DNA and nuclear proteins

Jinho Park, Kee Jun Kim, Kyoung Seong Choi, Dennis J. Grab, J. Stephen Dumler

Research output: Contribution to journalArticle

Abstract

Human granulocytic anaplasmosis (HGA) is caused by the obligate intracellular bacterium Anaplasma phagocytophilum. The bacterium infects, survives, propagates in, and alters neutrophil phenotype, indicating unique survival mechanisms. AnkA is the only known A. phagocytophilum component that gains access beyond neutrophil vacuoles and is transported to the infected host cell nucleus. The ability of native and recombinant AnkA to bind DNA and nuclear proteins from host HL-60 cells was assessed by the use of immunoprecipitation after cis-diamminedichloroplatinum (cis-DDP) DNA-protein crosslinking, by probing uninfected HL-60 cell nuclear lysates for AnkA binding, and by recovery and sequence analysis of immunoprecipitated DNA. AnkA binds HL-60 cell DNA as well as nuclear proteins of approximately 86, 53 and 25 kDa, whereas recombinant A. phagocytophilum Msp2 or control proteins do not. DNA immunoprecipitation reveals AnkA binding to a variety of target genes in the human genome, including genes that encode proteins with ATPase, tyrosine phosphatase and NADH dehydrogenase-like functions. These data indicate that AnkA could exert some effect on cells through binding to protein:DNA complexes in neutrophil nuclei. Whether AnkA binding leads to neutrophil functional alterations, and how such alterations might occur will depend upon definitive identification of binding partners and associated metabolic and biochemical pathways.

Original languageEnglish (US)
Pages (from-to)743-751
Number of pages9
JournalCellular Microbiology
Volume6
Issue number8
DOIs
StatePublished - Aug 2004

Fingerprint

Anaplasma phagocytophilum
Nuclear Proteins
Granulocytes
HL-60 Cells
Neutrophils
DNA
Immunoprecipitation
Genes
Anaplasmosis
Bacteria
NADH Dehydrogenase
Proteins
DNA-Binding Proteins
Human Genome
Vacuoles
Metabolic Networks and Pathways
Cell Nucleus
DNA Sequence Analysis
Phosphoric Monoester Hydrolases
Cisplatin

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Microbiology

Cite this

Anaplasma phagocytophilum AnkA binds to granulocyte DNA and nuclear proteins. / Park, Jinho; Kim, Kee Jun; Choi, Kyoung Seong; Grab, Dennis J.; Dumler, J. Stephen.

In: Cellular Microbiology, Vol. 6, No. 8, 08.2004, p. 743-751.

Research output: Contribution to journalArticle

Park, Jinho ; Kim, Kee Jun ; Choi, Kyoung Seong ; Grab, Dennis J. ; Dumler, J. Stephen. / Anaplasma phagocytophilum AnkA binds to granulocyte DNA and nuclear proteins. In: Cellular Microbiology. 2004 ; Vol. 6, No. 8. pp. 743-751.
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