A virulence-associated filamentous bacteriophage of Neisseria meningitidis increases host-cell colonisation

PLoS Pathogens

Xavier Nassif¹  Emmanuelle Bille¹  Daniel Euphrasie¹  Terry Brissac¹  Philippe Pelissier²  Anne Jamet²  Anna Larsen³  Julie Meyer³  Jean-Philippe Barnier³ 

[1] Institut Necker-Enfants Malades, INSERM U1151, CNRS UMR 8253, Paris, France;Service de Microbiologie, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France;Université Paris Descartes, Paris, France

关键词: Bacteriophages;    Epithelial cells;    Pili;    fimbriae;    Neisseria meningitidis;    Endothelial cells;    Bacterial pathogens;    Bacteria;    Meningococcal disease;   

DOI  :  10.1371/journal.ppat.1006495

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Neisseria meningitidis is a commensal of human nasopharynx. In some circumstances, this bacteria can invade the bloodstream and, after crossing the blood brain barrier, the meninges. A filamentous phage, designated MDAΦ for Meningococcal Disease Associated, has been associated with invasive disease. In this work we show that the prophage is not associated with a higher virulence during the bloodstream phase of the disease. However, looking at the interaction of N. meningitidis with epithelial cells, a step essential for colonization of the nasopharynx, we demonstrate that the presence of the prophage, via the production of viruses, increases colonization of encapsulated meningococci onto monolayers of epithelial cells. The analysis of the biomass covering the epithelial cells revealed that meningococci are bound to the apical surface of host cells by few layers of heavily piliated bacteria, whereas, in the upper layers, bacteria are non-piliated but surrounded by phage particles which (i) form bundles of filaments, and/or (ii) are in some places associated with bacteria. The latter are likely to correspond to growing bacteriophages during their extrusion through the outer membrane. These data suggest that, as the biomass increases, the loss of piliation in the upper layers of the biomass does not allow type IV pilus bacterial aggregation, but is compensated by a large production of phage particles that promote bacterial aggregation via the formation of bundles of phage filaments linked to the bacterial cell walls. We propose that MDAΦ by increasing bacterial colonization in the mucosa at the site-of-entry, increase the occurrence of diseases.

【 授权许可】

CC BY