Golovkine Guillaume, Faudry Eric, Bouillot Stéphanie, Elsen Sylvie, Attrée Ina, Huber Philippe
University Grenoble Alpes, Grenoble, France.
CNRS, ERL5261, Grenoble, France.
PLoS Pathog. 2016 Jan 4;12(1):e1005377. doi: 10.1371/journal.ppat.1005377. eCollection 2016 Jan.
To achieve systemic infection, bacterial pathogens must overcome the critical and challenging step of transmigration across epithelial barriers. This is particularly true for opportunistic pathogens such as Pseudomonas aeruginosa, an agent which causes nosocomial infections. Despite extensive study, details on the mechanisms used by this bacterium to transmigrate across epithelial tissues, as well as the entry sites it uses, remain speculative. Here, using real-time microscopy and a model epithelial barrier, we show that P. aeruginosa employs a paracellular transmigration route, taking advantage of altered cell-cell junctions at sites of cell division or when senescent cells are expelled from the cell layer. Once a bacterium transmigrates, it is followed by a cohort of bacteria using the same entry point. The basal compartment is then invaded radially from the initial penetration site. Effective transmigration and propagation require type 4 pili, the type 3 secretion system (T3SS) and a flagellum, although flagellum-deficient bacteria can occasionally invade the basal compartment from wounded areas. In the basal compartment, the bacteria inject the T3SS toxins into host cells, disrupting the cytoskeleton and focal contacts to allow their progression under the cells. Thus, P. aeruginosa exploits intrinsic host cell processes to breach the epithelium and invade the subcellular compartment.
为实现全身感染，细菌病原体必须克服跨越上皮屏障这一关键且具有挑战性的步骤。对于诸如铜绿假单胞菌这种引起医院感染的机会性病原体而言尤其如此。尽管已进行了广泛研究，但关于该细菌跨越上皮组织所使用的机制以及其进入位点的细节仍属推测。在此，我们利用实时显微镜和一个上皮屏障模型表明，铜绿假单胞菌采用细胞旁迁移途径，利用细胞分裂位点或衰老细胞从细胞层排出时细胞间连接的改变。一旦有细菌迁移，随后会有一群细菌利用相同的进入点。然后从初始穿透位点向基底腔进行径向侵袭。有效的迁移和繁殖需要4型菌毛、3型分泌系统（T3SS）和一根鞭毛，尽管缺乏鞭毛的细菌偶尔也能从受伤区域侵入基底腔。在基底腔中，细菌将T3SS毒素注入宿主细胞，破坏细胞骨架和黏着斑，以便它们在细胞下方行进。因此，铜绿假单胞菌利用宿主细胞的内在过程来突破上皮并侵入亚细胞腔。
