Hussain Muzaffar, Steinbacher Tim, Peters Georg, Heilmann Christine, Becker Karsten
Institute of Medical Microbiology, University Hospital of Münster, Münster, Germany.
Institute of Medical Microbiology, University Hospital of Münster, Münster, Germany; Interdisciplinary Centre of Clinical Research (IZKF), University Hospital of Münster, Münster, Germany.
Int J Med Microbiol. 2015 Jan;305(1):129-39. doi: 10.1016/j.ijmm.2014.11.010. Epub 2014 Nov 27.
Although it belongs to the group of coagulase-negative staphylococci, Staphylococcus lugdunensis has been known to cause aggressive courses of native and prosthetic valve infective endocarditis with high mortality similar to Staphylococcus aureus. In contrast to S. aureus, only little is known about the equipment of S. lugdunensis with virulence factors including adhesins and their role in mediating attachment to extracellular matrix and plasma proteins and host cells. In this study, we show that the multifunctional autolysin/adhesin AtlL of S. lugdunensis binds to the extracellular matrix and plasma proteins fibronectin, fibrinogen, and vitronectin as well as to human EA.hy926 endothelial cells. Furthermore, we demonstrate that AtlL also plays an important role in the internalization of S. lugdunensis by eukaryotic cells: The atlL-deficient mutant Mut17 adheres to and becomes internalized by eukaryotic cells to a lesser extent than the isogenic wild-type strain Sl253 and the complemented mutant Mut17 (pCUatlL) shows an increased internalization level in comparison to Mut17. Thus, surface localized AtlL that exhibits a broad binding spectrum also mediates the internalization of S. lugdunensis by eukaryotic cells. We therefore propose an internalization pathway for S. lugdunensis, in which AtlL plays a major role. Investigating the role of AtlL in biofilm formation of S. lugdunensis, Mut17 shows a significantly reduced ability for biofilm formation, which is restored in the complemented mutant. Thus, our data provide evidence for a significant role for AtlL in adherence and internalization processes as well as in biofilm formation of S. lugdunensis.
尽管路邓葡萄球菌属于凝固酶阴性葡萄球菌，但已知它会引发侵袭性的天然瓣膜和人工瓣膜感染性心内膜炎，其死亡率很高，与金黄色葡萄球菌相似。与金黄色葡萄球菌不同，对于路邓葡萄球菌携带包括黏附素在内的毒力因子的情况及其在介导与细胞外基质、血浆蛋白和宿主细胞黏附中的作用了解甚少。在本研究中，我们发现路邓葡萄球菌的多功能自溶素/黏附素AtlL可与细胞外基质、血浆蛋白纤连蛋白、纤维蛋白原和玻连蛋白以及人EA.hy926内皮细胞结合。此外，我们证明AtlL在路邓葡萄球菌被真核细胞内化过程中也起重要作用：与同基因野生型菌株Sl253相比，atlL缺陷型突变体Mut17被真核细胞黏附和内化的程度较低，而互补突变体Mut17（pCUatlL）与Mut17相比内化水平有所提高。因此，具有广泛结合谱的表面定位的AtlL也介导了路邓葡萄球菌被真核细胞内化。我们因此提出了一条路邓葡萄球菌的内化途径，其中AtlL起主要作用。研究AtlL在路邓葡萄球菌生物膜形成中的作用时，Mut17显示出生物膜形成能力显著降低，而在互补突变体中得以恢复。因此，我们的数据证明AtlL在路邓葡萄球菌的黏附、内化过程以及生物膜形成中起重要作用。
