Bille Emmanuelle, Meyer Julie, Jamet Anne, Euphrasie Daniel, Barnier Jean-Philippe, Brissac Terry, Larsen Anna, Pelissier Philippe, Nassif Xavier
Institut Necker-Enfants Malades, INSERM U1151, CNRS UMR 8253, Paris, France.
Université Paris Descartes, Paris, France.
PLoS Pathog. 2017 Jul 13;13(7):e1006495. doi: 10.1371/journal.ppat.1006495. eCollection 2017 Jul.
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.
脑膜炎奈瑟菌是人类鼻咽部的共生菌。在某些情况下，这种细菌可侵入血流，并在穿过血脑屏障后侵入脑膜。一种丝状噬菌体，命名为与脑膜炎球菌病相关的MDAΦ，已被发现与侵袭性疾病有关。在这项研究中，我们发现前噬菌体在疾病的血流阶段并不与更高的毒力相关。然而，观察脑膜炎奈瑟菌与上皮细胞的相互作用（这是在鼻咽部定植的一个关键步骤），我们证明前噬菌体的存在通过病毒的产生，增加了包膜脑膜炎球菌在上皮细胞单层上的定植。对覆盖上皮细胞的生物量分析表明，脑膜炎球菌通过几层大量菌毛化的细菌与宿主细胞的顶端表面结合，而在上层，细菌没有菌毛，但被噬菌体颗粒包围，这些噬菌体颗粒（i）形成丝状束，和/或（ii）在某些地方与细菌相关。后者可能对应于噬菌体在通过外膜挤出过程中的生长阶段。这些数据表明，随着生物量的增加，生物量上层菌毛的丧失不允许IV型菌毛细菌聚集，但通过大量产生噬菌体颗粒得到补偿，这些噬菌体颗粒通过形成与细菌细胞壁相连的噬菌体丝束促进细菌聚集。我们提出，MDAΦ通过增加在进入部位的粘膜中的细菌定植，增加了疾病的发生率。
