title: Neisserial Heparin Binding Antigen (NHBA) Contributes to the Adhesion of Neisseria meningitidis to Human Epithelial Cells.
abstract: Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein ubiquitously expressed by Neisseria meningitidis strains and an antigen of the Bexsero® vaccine. NHBA binds heparin through a conserved Arg-rich region that is the target of two proteases, the meningococcal NalP and human lactoferrin (hLf). In this work, in vitro studies showed that recombinant NHBA protein was able to bind epithelial cells and mutations of the Arg-rich tract abrogated this binding. All N-terminal and C-terminal fragments generated by NalP or hLf cleavage, regardless of the presence or absence of the Arg-rich region, did not bind to cells, indicating that a correct positioning of the Arg-rich region within the full length protein is crucial. Moreover, binding was abolished when cells were treated with heparinase III, suggesting that this interaction is mediated by heparan sulfate proteoglycans (HSPGs). N. meningitidis nhba knockout strains showed a significant reduction in adhesion to epithelial cells with respect to isogenic wild-type strains and adhesion of the wild-type strain was inhibited by anti-NHBA antibodies in a dose-dependent manner. Overall, the results demonstrate that NHBA contributes to meningococcal adhesion to epithelial cells through binding to HSPGs and suggest a possible role of anti-Bexsero® antibodies in the prevention of colonization.
authors: GSK Vaccines, Siena, Italy.
authors: Irene
authors: I
authors: Vacca
authors: GSK Vaccines, Siena, Italy.
authors: Elena
authors: E
authors: Del Tordello
authors: GSK Vaccines, Siena, Italy.
authors: Gianmarco
authors: G
authors: Gasperini
authors: GSK Vaccines, Siena, Italy.
authors: Alfredo
authors: A
authors: Pezzicoli
authors: GSK Vaccines, Siena, Italy.
authors: Martina
authors: M
authors: Di Fede
authors: GSK Vaccines, Siena, Italy.
authors: Silvia
authors: S
authors: Rossi Paccani
authors: GSK Vaccines, Siena, Italy.
authors: Sara
authors: S
authors: Marchi
authors: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors: Tsisti D
authors: TD
authors: Mubaiwa
authors: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors: Lauren E
authors: LE
authors: Hartley-Tassell
authors: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors: Michael P
authors: MP
authors: Jennings
authors: Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
authors: Kate L
authors: KL
authors: Seib
authors: GSK Vaccines, Siena, Italy.
authors: Vega
authors: V
authors: Masignani
authors: GSK Vaccines, Siena, Italy.
authors: Mariagrazia
authors: M
authors: Pizza
authors: GSK Vaccines, Siena, Italy.
authors: Davide
authors: D
authors: Serruto
authors: GSK Vaccines, Siena, Italy.
authors: Beatrice
authors: B
authors: Aricò
authors: GSK Vaccines, Siena, Italy.
authors: Isabel
authors: I
authors: Delany
mesh_terms: D000907:Antibodies, Bacterial / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology*; D055786:Gene Knockout Techniques; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008589:Meningococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control; D009154:Mutation; D009345:Neisseria meningitidis / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D019812:Heparan Sulfate Proteoglycans; C490098:LTF protein, human; D026901:Membrane Transport Proteins; C000620214:NHBA protein, Neisseria meningitidis; D011994:Recombinant Proteins; D006493:Heparin; D007781:Lactoferrin; C480853:NalP protein, Neisseria meningitidis; D012697:Serine Endopeptidases