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

Putten, J. P. M. Van; Paul, Souvik

doi:10.1002/j.1460-2075.1995.tb07208.x

Cited by 228 publications

(288 citation statements)

References 73 publications

(42 reference statements)

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“…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).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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Infections by Neisseria gonorrhoeae are increasingly common, are often caused by antibiotic-resistant strains, and can result in serious and lasting sequelae, prompting the reemergence of gonococcal disease as a leading global health concern. N. gonorrhoeae is a human-restricted pathogen that primarily colonizes urogenital mucosal surfaces. Disease progression varies greatly between the sexes: men usually present with symptomatic infection characterized by a painful purulent urethral discharge, while in women, the infection is often asymptomatic, with the most severe pathology occurring when the bacteria ascend from the lower genital tract into the uterus and fallopian tubes. Classical clinical studies demonstrated that clinically infectious strains uniformly express Opa adhesins; however, their specificities were unknown at the time. While in vitro studies have since identified CEACAM proteins as the primary target of Opa proteins, the gonococcal specificity for this human family of receptors has not been addressed in the context of natural infection. In this study, we characterize a collection of low-passage-number clinicalspecimen-derived N. gonorrhoeae isolates for Opa expression and assess their CEACAM-binding profiles. We report marked in vivo selection for expression of phase-variable Opa proteins that bind CEACAM1 and CEACAM5 but selection against expression of Opa variants that bind to the neutrophil-restricted decoy receptor CEACAM3. This is the first study showing phenotypic selection for distinct CEACAM-binding phenotypes in vivo, and it supports the opposing functions of CEACAMs that facilitate infection versus driving inflammation within the genital tract.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…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.…”

Section: Espite the Availability Of Effective Antibiotic Therapiesmentioning

confidence: 99%

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

Lee

Ostrowski

Gray-Owen

2008

The Journal of Immunology

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Neisseria gonorrhoeae colony opacity-associated (Opa) proteins bind to human carcinoembryonic antigen cellular adhesion molecules (CEACAM) found on host cells including T lymphocytes. Opa binding to CEACAM1 suppresses the activation of CD4+ T cells in response to a variety of stimuli. In this study, we use primary human CD4+ T cells isolated from peripheral blood to define the molecular events occurring subsequent to Opa-CEACAM1 binding. We establish that, in contrast to other cell types, T cells do not engulf N. gonorrhoeae upon CEACAM1 binding. Instead, the bacteria recruit CEACAM1 from intracellular stores and maintain it on the T cell surface. Upon TCR ligation, the co-engaged CEACAM1 becomes phosphorylated on tyrosine residues within the ITIMs apparent in the cytoplasmic domain. This allows the recruitment and subsequent activation of the src homology domain 2-containing tyrosine phosphatases SHP-1 and SHP-2 at the site of bacterial attachment, which prevents the normal tyrosine phosphorylation of the CD3ζ-chain and ZAP-70 kinase in response to TCR engagement. Combined, this dynamic response allows the bacteria to effectively harness the coinhibitory function of CEACAM1 to suppress the adaptive immune response at its earliest step.

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“…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).…”

Section: N-terminal and Repeat Region Domains Are Necessary Formentioning

confidence: 99%

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

Baron

Bolduc²,

Goldberg

et al. 2004

Journal of Biological Chemistry

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Group B Streptococcus (GBS) colonizes mucosal surfaces of the human gastrointestinal and gynecological tracts and causes disease in a wide range of patients. Invasive illness occurs after organisms traverse an epithelial boundary and enter deeper tissues. Previously we have reported that the alpha C protein (ACP) on the surface of GBS mediates GBS entry into ME180 cervical epithelial cells and GBS translocation across layers of these cells. We now demonstrate that ACP interacts with host cell glycosaminoglycan (GAG); the interaction of ACP with ME180 cells is inhibited if cells are pretreated with sodium chlorate, an inhibitor of sulfate incorporation, or with heparitinases. The interaction is also inhibited in the presence of soluble heparin or heparan sulfate or host cell-derived GAG. In addition, ACP binds soluble heparin specifically in inhibition and dot blot assays. After interaction with host GAG, soluble ACP enters ME180 cells and fractionates to the eukaryotic cell cytosol. These events are inhibited in cells pretreated with cytochalasin D or with Clostridium difficile toxin B. These data indicate that full-length ACP interacts with ME180 cell GAG and enters the eukaryotic cell cytosol by a mechanism that involves Rho GTPase-dependent actin rearrangements. We suggest that these molecular interactions drive ACP-mediated translocation of GBS across epithelial barriers, thereby facilitating invasive GBS infection.Streptococcus agalactiae (Group B Streptococcus, GBS) 1 has long been recognized as an important cause of infection in pregnant/peripartum women and neonates. A frequent colonizer of the human gastrointestinal and gynecological tracts, GBS has been noted more recently to cause a range of invasive syndromes in non-pregnant adults. Most commonly these patients have comorbid conditions, including malignancy, diabetes, and renal disease (1), that may predispose to bacterial invasion because of a loss of epithelial barrier protection in a chronically colonized site such as the rectum, vagina, cervix, urethra, skin, or pharynx. The molecular basis of the interaction between GBS and epithelial cells remains poorly understood.We have reported that the alpha C protein (ACP) on the surface of GBS interacts with epithelial cells. Expressed by many serotype Ia, Ib, and II GBS strains, ACP is the prototype for a family of Gram-positive surface proteins, the alpha-like proteins (Alps). Found on most GBS strains and some Enterococcus and group A Streptococcus strains, Alps share considerable sequence homology and common structural elements, including an N-terminal region, a series of tandem repeats of ϳ80 amino acids each, and a C-terminal region containing a cellwall anchor LPXTG motif common to several Gram-positive species. Despite the fact that these proteins may vary in size due to gene truncation within the repeat region (2), Alps elicit protective antibody in both adult and neonatal mouse models of GBS sepsis (3). In a neonatal mouse model of disease, deletion of the gene encoding ACP attenuates the virul...

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

Cited by 228 publications

References 73 publications

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

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

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

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

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