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The Great Bridge of Heparin: OpcA Binds to Heparin Eliciting an Interaction with Fibronectin Causing Meningitis
Author(s) -
Alfaro Monica,
Chavez Edwin,
Grosjean Ellie,
Ibrahim Fady,
Martinez Denise,
Munoz Juan,
Nguyen John,
Tandazo Andres,
Stubbs Tamica,
Colton Shan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb156
Subject(s) - meninges , transcytosis , fibronectin , bacterial adhesin , meningitis , microbiology and biotechnology , immunology , laminin , biology , immune system , medicine , extracellular matrix , receptor , pathology , endocytosis , genetics , gene , escherichia coli , psychiatry
Meningitis is an inflammation of the meninges, membranes that cover the brain and spinal cord. It can be caused by several pathogenic agents existing in the nasopharynx region of humans. The gram‐negative bacterium, Neisseria meningitidis , confers pathogenicity when it sheds its capsule, crosses the epithelium layer and enters the bloodstream via transcytosis. Upon entry, the bacterium reforms its capsule and modulates its adhesins, such as pili and opacity proteins (Opc) to avoid the hosts' immune response and to adhere to epithelial cells of the meninges. While en route to the meninges, lipopolysaccarides adhesins may induce septicemia by causing toxic damage to cells. Upon arrival to its host meninges, it wreaks havoc by utilizing basic residues on the crevice of its OpcA protein to increase interaction with polysaccarides and heparin, a receptor on the host's meninges. This bond forms a bridge enabling OpcA to bind with fibronectin inducing interaction with integrins, aiding with cellular adhesion to the extracellular matrix during transcytosis. By understanding the structure of OpcA we can inhibit the interaction between N.meningitis and host cells with a vaccine that can potentially prevent meningitis. The E.E. Waddell SMART (Students Modeling A Research Topic) Team along with MSOE built accurate models of OpcA, heparin, and fibronectin using 3D printing. Supported by a grant from NIH‐NCRR‐SEPA