A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies

Maria Jose Uria, Qian Zhang, Yanwen Li, Angel Chan, Rachel M. Exley, Bridget Gollan, Hannah Chan, Ian Feavers, Andy Yarwood, Raquel Abad, Raymond Borrow, Roland A. Fleck, Barbara Mulloy, Julio A. Vazquez, Christoph M. Tang

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

The presence of serum bactericidal antibodies is a proven correlate of protection against systemic infection with the important human pathogen Neisseria meningitidis. We have identified three serogroup C N. meningitidis (MenC) isolates recovered from patients with invasive meningococcal disease that resist killing by bactericidal antibodies induced by the MenC conjugate vaccine. None of the patients had received the vaccine, which has been successfully introduced in countries in North America and Europe. The increased resistance was not caused by changes either in lipopolysaccharide sialylation or acetylation of the α2-9-linked polysialic acid capsule. Instead, the resistance of the isolates resulted from the presence of an insertion sequence, IS 1301, in the intergenic region (IGR) between the sia and ctr operons, which are necessary for capsule biosynthesis and export, respectively. The insertion sequence led to an increase in the transcript levels of surrounding genes and the amount of capsule expressed by the strains. The increased amount of capsule was associated with down-regulation of the alternative pathway of complement activation, providing a generic mechanism by which the bacterium protects itself against bactericidal antibodies. The strains with IS 1301 in the IGR avoided complement-mediated lysis in the presence of bactericidal antibodies directed at the outer membrane protein, PorA, or raised against whole cells.

Original languageEnglish
Pages (from-to)1423-1434
Number of pages12
JournalJournal of Experimental Medicine
Volume205
Issue number6
DOIs
Publication statusPublished - 9 Jun 2008
Externally publishedYes

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