University of Leicester
Browse
mic001305.pdf (1.73 MB)

Variable disruption of epithelial monolayers by Neisseria meningitidis carriage isolates of the hypervirulent MenW cc11 and MenY cc23 lineages

Download (1.73 MB)
journal contribution
posted on 2023-04-28, 15:01 authored by N Dave, RS Albiheyri, JJ Wanford, LR Green, NJ Oldfield, DPJ Turner, L Martinez-Pomares, CD Bayliss
Colonization of mucosal tissues by Neisseria meningitidis requires adhesion mediated by the type IV pilus and multiple outer-membrane proteins. Penetration of the mucosa and invasion of epithelial cells are thought to contribute to host persistence and invasive disease. Using Calu-3 cell monolayers grown at an air–liquid interface, we examined adhesion, invasion and monolayer disruption by carriage isolates of two clonal complexes of N. meningitidis. Carriage isolates of both the serogroup Y cc23 and the hypervirulent serogroup W cc11 lineages exhibited high levels of cellular adhesion, and a variable disruption phenotype across independent isolates. Inactivation of the gene encoding the main pilus sub-unit in multiple cc11 isolates abrogated both adhesive capacity and ability to disrupt epithelial monolayers. Contrastingly, inactivation of the phase-variable opa or nadA genes reduced adhesion and invasion, but not disruption of monolayer integrity. Adherence of tissue-disruptive meningococci correlated with loss of staining for the tight junction protein, occludin. Intriguingly, in a pilus-negative strain background, we observed compensatory ON switching of opa genes, which facilitated continued adhesion. We conclude that disruption of epithelial monolayers occurs in multiple meningococcal lineages but can vary during carriage and is intimately linked to pilus-mediated adhesion.

Funding

Medical Research Council (IMPACT) studentship

MICA: Does phase variation contribute to virulence and immune evasion of Neisseria meningitidis?

Medical Research Council

Find out more...

History

Author affiliation

Department of Genetics and Genome Biology, University of Leicester

Version

  • VoR (Version of Record)

Published in

Microbiology

Volume

169

Issue

2

Publisher

Microbiology Society

issn

1350-0872

eissn

1465-2080

Copyright date

2023

Available date

2023-04-28

Spatial coverage

England

Language

eng

Usage metrics

    University of Leicester Publications

    Categories

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC