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Volume 169, Issue 2

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

Abstract

Colonization of mucosal tissues by 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 . 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 or 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 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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): air–liquid interface , meningococcus , MenW , Neisseria meningitidis , opa and phase variation
Funding
This study was supported by the:
  • Medical Research Council (Award IMPACT studentship)
    • Principle Award Recipient: JosephJ. Wanford
  • Medical Research Council (Award MR/M020193/1)
    • Principle Award Recipient: ChristopherDavid Bayliss
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-02-23
2024-05-14
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Variable disruption of epithelial monolayers by Neisseria meningitidis carriage isolates of the hypervirulent MenW cc11 and MenY cc23 lineages
Microbiology 169, 001305 (2023); https://doi.org/10.1099/mic.0.001305
/content/journal/micro/10.1099/mic.0.001305
/content/journal/micro/10.1099/mic.0.001305
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