Characterization of Neisseria meningitidis Isolates That Do Not Express the Virulence Factor and Vaccine Antigen Factor H Binding Protein

Author:

Lucidarme Jay1,Tan Lionel2,Exley Rachel M.2,Findlow Jamie1,Borrow Ray13,Tang Christoph M.2

Affiliation:

1. 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

2. Centre for Molecular Microbiology and Infection, Department of Microbiology, Flowers Building, Imperial College London, London SW7 2AZ, United Kingdom

3. University of Manchester, Inflammation Sciences Research Group, School of Translational Medicine, Stopford Building, Manchester M13 9PL, United Kingdom

Abstract

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.

Publisher

American Society for Microbiology

Subject

Microbiology (medical),Clinical Biochemistry,Immunology,Immunology and Allergy

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