The influence of IS1301 in the capsule biosynthesis locus on meningococcal carriage and disease.

Elisabeth Kugelberg,Jay Lucidarme,Martin C J Maiden,Christopher Farrance,Bridget Gollan,Ray Borrow,Ana Belén Ibarz-Pavón,Christoph M Tang,Holly Bratcher

doi:10.1371/journal.pone.0009413

Elisabeth Kugelberg, Jay Lucidarme + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0009413

Copy DOI

Abstract

Previously we have shown that insertion of IS1301 in the sia/ctr intergenic region (IGR) of serogroup C Neisseria meningitidis (MenC) isolates from Spain confers increased resistance against complement-mediated killing. Here we investigate the significance of IS1301 in the same location in N. meningitidis isolates from the UK. PCR and sequencing was used to screen a collection of more than 1500 meningococcal carriage and disease isolates from the UK for the presence of IS1301 in the IGR. IS1301 was not identified in the IGR among vaccine failure strains but was frequently found in serogroup B isolates (MenB) from clonal complex 269 (cc269). Almost all IS1301 insertions in cc269 were associated with novel polymorphisms, and did not change capsule expression or resistance to human complement. After excluding sequence types (STs) distant from the central genotype within cc269, there was no significant difference for the presence of IS1301 in the IGR of carriage isolates compared to disease isolates. Isolates with insertion of IS1301 in the IGR are not responsible for MenC disease in UK vaccine failures. Novel polymorphisms associated with IS1301 in the IGR of UK MenB isolates do not lead to the resistance phenotype seen for IS1301 in the IGR of MenC isolates.

Highlights

The exclusively human pathogen Neisseria meningitidis causes serious diseases including septicaemia and bacterial meningitis.it is primarily a commensal of the human nasopharynx in around 10% of healthy individuals [1,2]
As an serum bactericidal assays (SBA) titre of,8 is a marker of protective immunity [13,14], we examined MenC isolates from individuals from the UK with meningococcal disease who had completed a course of the MenC conjugate vaccine [11,15]
The presence of IS1301 in the sia/ctr intergenic region (IGR) of MenC sequence types (STs)-11 enhances capsule expression and resistance against bactericidal antibodies elicited by the MenC conjugate vaccine [6]

Summary

Introduction

The exclusively human pathogen Neisseria meningitidis causes serious diseases including septicaemia and bacterial meningitis. It is primarily a commensal of the human nasopharynx in around 10% of healthy individuals [1,2]. The bacterium overcomes host defences, especially the complement system, and causes bloodstream infection, septic shock and/or meningitis. Isolates are categorised into sequence types (STs) based on sequences of seven housekeeping genes [4]. Most disease is caused by a limited number of genotypes, while other genotypes seldom invade the bloodstream [5]. Clonal complexes (cc) are groupings of STs with similar allelic profiles typically sharing at least 4–5 loci (http://pubmlst.org/neisseria)

Methods

Results

Conclusion