Affiliation:
1. Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, School of Medicine, Richmond, Virginia, USA
2. Research Complex for Medical Frontiers, Aichi Medical University, Yazako, Nagakute, Japan
Abstract
ABSTRACT
Anaplasma marginale
causes bovine anaplasmosis, a debilitating and potentially fatal tick-borne infection of cattle. Because
A. marginale
is an obligate intracellular organism, its adhesins that mediate entry into host cells are essential for survival. Here, we demonstrate that
A. marginale
outer membrane protein A (AmOmpA; AM854) contributes to the invasion of mammalian and tick host cells. AmOmpA exhibits predicted structural homology to OmpA of
A. phagocytophilum
(ApOmpA), an adhesin that uses key lysine and glycine residues to interact with α2,3-sialylated and α1,3-fucosylated glycan receptors, including 6-sulfo-sialyl Lewis x (6-sulfo-sLe
x
). Antisera against AmOmpA or its predicted binding domain inhibits
A. marginale
infection of host cells. Residues G55 and K58 are contributory, and K59 is essential for recombinant AmOmpA to bind to host cells. Enzymatic removal of α2,3-sialic acid and α1,3-fucose residues from host cell surfaces makes them less supportive of AmOmpA binding. AmOmpA is both an adhesin and an invasin, as coating inert beads with it confers adhesiveness and invasiveness. Recombinant forms of AmOmpA and ApOmpA competitively antagonize
A. marginale
infection of host cells, but a monoclonal antibody against 6-sulfo-sLe
x
fails to inhibit AmOmpA adhesion and
A. marginale
infection. Thus, the two OmpA proteins bind related but structurally distinct receptors. This study provides a detailed understanding of AmOmpA function, identifies its essential residues that can be targeted by blocking antibody to reduce infection, and determines that it binds to one or more α2,3-sialylated and α1,3-fucosylated glycan receptors that are unique from those targeted by ApOmpA.
Funder
Stephen and Alexandra Cohen Foundation
HHS | NIH | National Institute of Allergy and Infectious Diseases
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
23 articles.
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