| Autor: |
Dave N; Department of Genetics and Genome Biology, University of Leicester, Leicester, UK., Albiheyri RS; School of Life Sciences, University of Nottingham, Nottingham, UK.; Present address: Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Wanford JJ; Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.; Present address: Department of Infectious Disease, King's College, London, UK., Green LR; Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.; Present address: Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK., Oldfield NJ; School of Life Sciences, University of Nottingham, Nottingham, UK., Turner DPJ; School of Life Sciences, University of Nottingham, Nottingham, UK., Martinez-Pomares L; School of Life Sciences, University of Nottingham, Nottingham, UK., Bayliss CD; Department of Genetics and Genome Biology, University of Leicester, Leicester, UK. |
| Abstrakt: |
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. |
