title: Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.
abstract: Neisseria meningitidis remains a leading cause of bacterial sepsis and meningitis. Complement is a key component of natural immunity against this important human pathogen, which has evolved multiple mechanisms to evade complement-mediated lysis. One approach adopted by the meningococcus is to recruit a human negative regulator of the complement system, factor H (fH), to its surface via a lipoprotein, factor H binding protein (fHbp). Additionally, fHbp is a key antigen in vaccines currently being evaluated in clinical trials. Here we characterize strains of N. meningitidis from several distinct clonal complexes which do not express fHbp; all strains were recovered from patients with disseminated meningococcal disease. We demonstrate that these strains have either a frameshift mutation in the fHbp open reading frame or have entirely lost fHbp and some flanking sequences. No fH binding was detected to other ligands among the fHbp-negative strains. The implications of these findings for meningococcal pathogenesis and prevention are discussed.
authors.affiliation: Vaccine Evaluation Unit, Health Protection Agency, North West Regional Laboratory, P.O. Box 209, Clinical Sciences Building II, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom.
authors.forename: Jay
authors.initials: J
authors.lastname: Lucidarme
authors.forename: Lionel
authors.initials: L
authors.lastname: Tan
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Exley
authors.forename: Jamie
authors.initials: J
authors.lastname: Findlow
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Tang
mesh_terms: D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D001428:Bacterial Vaccines / Q000096:biosynthesis* / Q000235:genetics; D016368:Frameshift Mutation; D017353:Gene Deletion; D006801:Humans; D008589:Meningococcal Infections / Q000382:microbiology*; D009345:Neisseria meningitidis / Q000235:genetics / Q000302:isolation & purification*; D037521:Virulence Factors / Q000096:biosynthesis* / Q000172:deficiency
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D037521:Virulence Factors; C484699:factor H-binding protein, Neisseria meningitidis