Binding of syndecan-like cell surface proteoglycan receptors is required for Neisseria gonorrhoeae entry into human mucosal cells.

Abstract

Bacterial invasion of human mucosal cells is considered to be a primary event in the pathogenesis of a gonococcal infection. Here we report that cell surface heparan sulfate proteoglycans may play a role in the establishment of an infection, by functioning as receptors for the invasion‐promoting gonococcal opacity protein adhesin. Chemical modification and enzymatic removal of proteoglycan receptors from cultured epithelial cells abolished opacity protein‐associated gonococcal invasion, and mutant cell lines defective in proteoglycan synthesis were poor substrates for gonococcal attachment. The addition of purified receptor and receptor analogues totally blocked gonococcal entry into the cells. Heparin‐affinity chromatography and receptor binding assays using recombinant bacteria producing defined opacity proteins and reconstituted receptor or purified receptor fragments as probes, identified one particular member of the opacity protein family (MS11‐Opa30) as the primary ligand for this novel class of receptors for bacteria. Heparan sulfate proteoglycans with gonococcal binding activity were purified from various cell types derived from target tissues of gonococcal infection, including ME‐180 endocervical cells and primary cultures of human corneal epithelium. The physico‐chemical properties of the receptor indicate that it may belong to the syndecan proteoglycan family.

Selection for a CEACAM Receptor-Specific Binding Phenotype during Neisseria gonorrhoeae Infection of the Human Genital Tract

“…Its narrow host range is largely defined by its adhesin proteins and immune evasion mechanisms, which are specific for human cellular receptors and serum proteins (59). Pilus facilitates initial bacterial attachment to the urogenital mucosa (4), where other adhesins can then confer a tighter secondary binding to epithelium-expressed receptors (3,18,58,59). Of these, the Opa proteins mediate tight adherence and transcytosis to the subepithelial space (25,26).…”

CEACAM1 Dynamics during Neisseria gonorrhoeae Suppression of CD4+ T Lymphocyte Activation

“…Although certain Opa variants bind to heparan sulfate proteoglycan receptors (13)(14)(15), most are specific for members of the carcinoembryonic Ag-related cellular adhesion molecule (CEACAM) family of receptors (16 -22). CEACAMs are members of the Ig superfamily consisting of an amino-terminal Ig variable domain-like region followed by a variable number of Ig constant-like domains.…”

Alpha C Protein of Group B Streptococcus Binds Host Cell Surface Glycosaminoglycan and Enters Cells by an Actin-dependent Mechanism

“…Proteoglycans participate in diverse processes, including cell adhesion, growth factor signaling, tumor biology, hemostasis, and lipid metabolism. These molecules also mediate interaction between epithelial cells and numerous pathogens, including viruses (such as human immunodeficiency virus (10), herpes simplex virus (31), human papilloma virus (9), and parainfluenza 3 (7)), spirochetes (such as Borrelia burgdorferi (32)), parasites (such as Trypanosoma cruzi (8)), and bacteria (such as Neisseria gonorrhoeae (11) and Listeria monocytogenes (6)). In some cases, GAG serves as a co-receptor, modulating the interaction of an extracellular ligand with other host cell surface structures by altering ligand concentration, stability, or conformation, or by promoting ligand or receptor oligomerization (33).…”