title: Characterization of a sialic acid- and P-selectin glycoprotein ligand-1-independent adhesin activity in the granulocytotropic bacterium Anaplasma phagocytophilum.
abstract: Anaplasma phagocytophilum, the aetiologic agent of human granulocytic anaplasmosis, is an obligate intracellular bacterium that colonizes neutrophils and neutrophil precursors. The granulocytotropic bacterium uses multiple adhesins that cooperatively bind to the N-terminal region of P-selectin glycoprotein ligand-1 (PSGL-1) and to sialyl Lewis x (sLe(x)) expressed on myeloid cell surfaces. Recognition of sLe(x) occurs through interactions with alpha2,3-sialic acid and alpha1,3-fucose. It is unknown whether other bacteria-host cell interactions are involved. In this study, we have enriched for A. phagocytophilum organisms that do not rely on sialic acid for cellular adhesion and entry by maintaining strain NCH-1 in HL-60 cells that are severely undersialylated. The selected bacteria, termed NCH-1A, also exhibit lessened dependencies on PSGL-1 and alpha1,3-fucose. Optimal adhesion and invasion by NCH-1A require interactions with the known determinants (sialic acid, PSGL-1 and alpha1,3-fucose), but none of them is absolutely necessary. NCH-1A binding to sLe(x)-modified PSGL-1 requires recognition of the known determinants in the same manners as other A. phagocytophilum strains. These data suggest that A. phagocytophilum expresses a separate adhesin from those targeting sialic acid, alpha1,3-fucose and the N-terminal region of PSGL-1. We propose that NCH-1A upregulates expression of this adhesin.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Dexter V
authors.initials: DV
authors.lastname: Reneer
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Kearns
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Yago
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sims
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
authors.forename: Rodger P
authors.initials: RP
authors.lastname: McEver
authors.forename: Jason A
authors.initials: JA
authors.lastname: Carlyon
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism*; D041081:Anaplasma phagocytophilum / Q000378:metabolism* / Q000472:pathogenicity; D001422:Bacterial Adhesion; D005643:Fucose / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D005643:Fucose; D019158:N-Acetylneuraminic Acid