title: Enterococcus faecalis aggregation substance promotes opsonin-independent binding to human neutrophils via a complement receptor type 3-mediated mechanism.
abstract: Enterococcus faecalis aggregation substance (AS) mediates efficient adhesion between bacteria, thereby facilitating plasmid exchange as an integral part of a bacterial sex pheromone system. We examined the interaction of AS-bearing E. faecalis with human neutrophils (PMNs), an important component of the host defense system. AS promoted a markedly increased opsonin-independent bacterial binding to PMNs. Adhesion was dependent on the expression of the enterococcal Asc10 protein, which contains two Arg-Gly-Asp (RGD) sequences, and addition of exogenous RGD-containing peptides inhibited AS-mediated binding by 66%. AS-mediated adhesion was inhibited by 85% by anti-human complement receptor type 3 (CR3) monoclonal antibodies or by use of PMNs from a patient with leukocyte adhesion deficiency. However, AS-bearing E. faecalis cells were unable to bind to CHO-Mac-1 cells, expressing functionally active CR3, suggesting the potential need for additional PMN surface receptors for bacterial adhesion. Monoclonal antibodies against integrin-associated protein (CD47) and L-selectin, both of which may interact with CR3 and bind to ligands on E. faecalis, also inhibited AS-dependent binding. The non-opsonic binding of E. faecalis to PMNs may play an important role in this organism's pathogenesis.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine and Center for the Study of Emerging and Reemerging Pathogens, University of Texas Medical School, Houston, TX 77030, USA.
authors.forename: N N
authors.initials: NN
authors.lastname: Vanek
authors.forename: S I
authors.initials: SI
authors.lastname: Simon
authors.forename: K
authors.initials: K
authors.lastname: Jacques-Palaz
authors.forename: M M
authors.initials: MM
authors.lastname: Mariscalco
authors.forename: G M
authors.initials: GM
authors.lastname: Dunny
authors.forename: R M
authors.initials: RM
authors.lastname: Rakita
mesh_terms: D018829:Adhesins, Bacterial / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D001422:Bacterial Adhesion / Q000187:drug effects; D001426:Bacterial Proteins / Q000276:immunology; D051928:CD47 Antigen; D016466:CHO Cells; D002352:Carrier Proteins / Q000276:immunology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008565:Membrane Proteins / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000382:microbiology* / Q000648:ultrastructure; D009842:Oligopeptides / Q000494:pharmacology / Q000502:physiology; D009895:Opsonin Proteins / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001426:Bacterial Proteins; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D009842:Oligopeptides; D009895:Opsonin Proteins; D019030:Receptors, Vitronectin; C083493:Sec10 protein, Enterococcus faecalis; C071729:Asc10 protein, Enterococcus faecalis; C047981:arginyl-glycyl-aspartic acid