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Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo
PLoS Pathogens ( IF 5.5 ) Pub Date : 2018-03-09 , DOI: 10.1371/journal.ppat.1006925
Kaiyi Zhang , Ambre Riba , Monika Nietschke , Natalia Torow , Urska Repnik , Andreas Pütz , Marcus Fulde , Aline Dupont , Michael Hensel , Mathias Hornef

Effector molecules translocated by the Salmonella pathogenicity island (SPI)1-encoded type 3 secretion system (T3SS) critically contribute to the pathogenesis of human Salmonella infection. They facilitate internalization by non-phagocytic enterocytes rendering the intestinal epithelium an entry site for infection. Their function in vivo has remained ill-defined due to the lack of a suitable animal model that allows visualization of intraepithelial Salmonella. Here, we took advantage of our novel neonatal mouse model and analyzed various bacterial mutants and reporter strains as well as gene deficient mice. Our results demonstrate the critical but redundant role of SopE2 and SipA for enterocyte invasion, prerequisite for transcriptional stimulation and mucosal translocation in vivo. In contrast, the generation of a replicative intraepithelial endosomal compartment required the cooperative action of SipA and SopE2 or SipA and SopB but was independent of SopA or host MyD88 signaling. Intraepithelial growth had no critical influence on systemic spread. Our results define the role of SPI1-T3SS effector molecules during enterocyte invasion and intraepithelial proliferation in vivo providing novel insight in the early course of Salmonella infection.



中文翻译:

体内沙门氏菌肠细胞侵袭和细胞内增殖的最低SPI1-T3SS效应子需求

沙门氏菌致病岛(SPI)1编码的3型分泌系统(T3SS)转运的效应分子在人类沙门氏菌感染的发病机理中起关键作用。它们促进非吞噬性肠上皮细胞的内在化,从而使肠上皮成为感染的进入位点。由于缺乏合适的动物模型,无法可视化上皮内沙门氏菌,因此它们在体内的功能仍不清楚。在这里,我们利用了我们的新型新生小鼠模型,并分析了各种细菌突变体和报告基因菌株以及基因缺陷小鼠。我们的结果证明了SopE 2的关键但多余的作用和SipA用于肠细胞的侵袭,是体内转录刺激和粘膜易位的前提条件。相比之下,复制性上皮细胞内体区室的产生需要SipA和SopE 2或SipA和SopB的协同作用,但独立于SopA或宿主MyD88信号传导。上皮内生长对全身扩散没有关键影响。我们的研究结果确定了SPI1-T3SS效应分子在体内肠细胞侵袭和上皮内增殖过程中的作用,为沙门氏菌感染的早期过程提供了新的见识。

更新日期:2018-03-10
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