Horstmann Julia A, Zschieschang Erik, Truschel Theresa, de Diego Juana, Lunelli Michele, Rohde Manfred, May Tobias, Strowig Till, Stradal Theresia, Kolbe Michael, Erhardt Marc
Junior Research Group Infection Biology of Salmonella, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Department for Structural Infection Biology, Center for Structural Systems Biology, Hamburg, Germany.
Cell Microbiol. 2017 Aug;19(8). doi: 10.1111/cmi.12739. Epub 2017 Apr 18.
The flagellum is a sophisticated nanomachine and an important virulence factor of many pathogenic bacteria. Flagellar motility enables directed movements towards host cells in a chemotactic process, and near-surface swimming on cell surfaces is crucial for selection of permissive entry sites. The long external flagellar filament is made of tens of thousands subunits of a single protein, flagellin, and many Salmonella serovars alternate expression of antigenically distinct flagellin proteins, FliC and FljB. However, the role of the different flagellin variants during gut colonisation and host cell invasion remains elusive. Here, we demonstrate that flagella made of different flagellin variants display structural differences and affect Salmonella's swimming behaviour on host cell surfaces. We observed a distinct advantage of bacteria expressing FliC-flagella to identify target sites on host cell surfaces and to invade epithelial cells. FliC-expressing bacteria outcompeted FljB-expressing bacteria for intestinal tissue colonisation in the gastroenteritis and typhoid murine infection models. Intracellular survival and responses of the host immune system were not altered. We conclude that structural properties of flagella modulate the swimming behaviour on host cell surfaces, which facilitates the search for invasion sites and might constitute a general mechanism for productive host cell invasion of flagellated bacteria.
鞭毛是一种精密的纳米机器，也是许多病原菌的重要毒力因子。鞭毛运动能使细菌在趋化过程中朝着宿主细胞定向移动，而在细胞表面附近游动对于选择合适的侵入位点至关重要。长长的外部鞭毛丝由数万个单一蛋白质鞭毛蛋白的亚基组成，许多沙门氏菌血清型会交替表达抗原性不同的鞭毛蛋白FliC和FljB。然而，不同鞭毛蛋白变体在肠道定殖和宿主细胞侵袭过程中的作用仍不清楚。在此，我们证明由不同鞭毛蛋白变体组成的鞭毛存在结构差异，并影响沙门氏菌在宿主细胞表面的游动行为。我们观察到表达FliC鞭毛的细菌在识别宿主细胞表面靶位点和侵入上皮细胞方面具有明显优势。在肠胃炎和伤寒小鼠感染模型中，表达FliC的细菌在肠道组织定殖方面胜过表达FljB的细菌。细胞内存活情况以及宿主免疫系统的反应未发生改变。我们得出结论，鞭毛的结构特性调节了在宿主细胞表面的游动行为，这有助于寻找侵入位点，可能构成了有鞭毛细菌有效侵入宿主细胞的一般机制。
