PDF(Pubmed)
Abstract：
The intestinal pathogen Salmonella enterica rapidly enters the bloodstream after the invasion of intestinal epithelial cells, but how Salmonella breaks through the gut-vascular barrier is largely unknown. Here, we report that Salmonella enters the bloodstream through intestinal CX3CR1+ macrophages during early infection. Mechanistically, Salmonella induces the migration/invasion properties of macrophages in a manner dependent on host cell actin and on the pathogen effector SteC. SteC recruits host myosin light chain protein Myl12a and phosphorylates its Ser19 and Thr20 residues. Myl12a phosphorylation results in actin rearrangement, and enhanced migration and invasion of macrophages. SteC is able to utilize a wide range of NTPs other than ATP to phosphorylate Myl12a. We further solved the crystal structure of SteC, which suggests an atypical dimerization-mediated catalytic mechanism. Finally, in vivo data show that SteC-mediated cytoskeleton manipulation is crucial for Salmonella breaching the gut vascular barrier and spreading to target organs.
摘要：
肠道致病菌肠道沙门氏菌侵入肠道上皮细胞后迅速进入血液,但沙门氏菌是如何突破肠道血管屏障的，在很大程度上是未知的。这里,我们报道沙门氏菌在感染早期通过肠道CX3CR1+巨噬细胞进入血液。机械上,沙门氏菌以依赖于宿主细胞肌动蛋白和病原体效应物SteC的方式诱导巨噬细胞的迁移/侵袭特性。SteC募集宿主肌球蛋白轻链蛋白Myl12a并磷酸化其Ser19和Thr20残基。Myl12a磷酸化导致肌动蛋白重排，增强巨噬细胞的迁移和侵袭。SteC能够利用除ATP以外的多种NTP来磷酸化Myl12a。我们进一步解决了SteC的晶体结构，这表明了非典型的二聚化介导的催化机理。最后,体内数据表明，SteC介导的细胞骨架操作对于沙门氏菌突破肠道血管屏障并扩散到靶器官至关重要。
