Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.

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 recrui...

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Автори: Lucidarme, J, Tan, L, Exley, R, Findlow, J, Borrow, R, Tang, C
Формат: Journal article
Мова:English
Опубліковано: 2011
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author Lucidarme, J
Tan, L
Exley, R
Findlow, J
Borrow, R
Tang, C
author_facet Lucidarme, J
Tan, L
Exley, R
Findlow, J
Borrow, R
Tang, C
author_sort Lucidarme, J
collection OXFORD
description 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.
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spelling oxford-uuid:3b801ec3-a746-49f8-8c8d-94f19cdeee4d2022-03-26T14:08:03ZCharacterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3b801ec3-a746-49f8-8c8d-94f19cdeee4dEnglishSymplectic Elements at Oxford2011Lucidarme, JTan, LExley, RFindlow, JBorrow, RTang, CNeisseria 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.
spellingShingle Lucidarme, J
Tan, L
Exley, R
Findlow, J
Borrow, R
Tang, C
Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.
title Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.
title_full Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.
title_fullStr Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.
title_full_unstemmed Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.
title_short Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor H binding protein.
title_sort characterization of neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen factor h binding protein
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