Structurally distinct requirements for binding of P-selectin glycoprotein ligand-1 and sialyl Lewis x to Anaplasma phagocytophilum and P-selectin

J Biol Chem. 2003 Sep 26;278(39):37987-97. doi: 10.1074/jbc.M305778200. Epub 2003 Jul 7.


Colonization of neutrophils by the bacterium Anaplasma phagocytophilum causes the disease human granulocytic ehrlichiosis. The pathogen also infects mice, its natural host. Like binding of P-selectin, binding of A. phagocytophilum to human neutrophils requires expression of P-selectin glycoprotein ligand-1 (PSGL-1) and alpha1-3-fucosyltransferases that construct the glycan determinant sialyl Lewis x (sLex). Binding of A. phagocytophilum to murine neutrophils, however, requires expression of alpha1-3-fucosyltransferases but not PSGL-1. To further characterize the molecular features that A. phagocytophilum recognizes, we measured bacterial binding to microspheres bearing specific glycoconjugates or to cells expressing human PSGL-1 and particular glycosyltransferases. Like P-selectin, A. phagocytophilum bound to purified human PSGL-1 and to glycopeptides modeled after the N terminus of human PSGL-1 that presented sLex on an O-glycan. Unlike P-selectin, A. phagocytophilum bound to glycopeptides that contained sLex but lacked tyrosine sulfation or a specific core-2 orientation of sLex on the O-glycan. A. phagocytophilum bound only to glycopeptides that contained a short amino acid sequence found in the N-terminal region of human but not murine PSGL-1. Unlike P-selectin, A. phagocytophilum bound to cells expressing PSGL-1 in cooperation with sLex on both N-and O-glycans. Moreover, bacteria bound to microspheres coupled independently with glycopeptide lacking sLex and with sLex lacking peptide. These results demonstrate that, unlike P-selectin, A. phagocytophilum binds cooperatively to a nonsulfated N-terminal peptide in human PSGL-1 and to sLex expressed on PSGL-1 or other glycoproteins. Distinct bacterial adhesins may mediate these cooperative interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adhesins, Bacterial / physiology
  • Amino Acid Sequence
  • Anaplasma phagocytophilum / physiology*
  • Animals
  • Bacterial Adhesion
  • Humans
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Microspheres
  • Molecular Sequence Data
  • Oligosaccharides / chemistry*
  • Oligosaccharides / metabolism*
  • P-Selectin / metabolism*
  • Sialyl Lewis X Antigen
  • Structure-Activity Relationship
  • Tyrosine / metabolism


  • Adhesins, Bacterial
  • Membrane Glycoproteins
  • Oligosaccharides
  • P-Selectin
  • P-selectin ligand protein
  • Sialyl Lewis X Antigen
  • Tyrosine