PDF(Pubmed)
Abstract：
Extraintestinal pathogenic Escherichia coli (ExPEC) is one of the leading causes of bloodstream infections in a broad spectrum of birds and mammals, thus poses a great threat to public health, while its underlying mechanism causing sepsis is not fully understood. Here we reported a high virulent ExPEC strain PU-1, which has a robust ability to colonize within host bloodstream, while induced a low level of leukocytic activation. Two serine protease autotransporters of Enterobacteriaceae (SPATEs), VatPU-1 and TshPU-1, were found to play critical roles for the urgent blood infection of strain PU-1. Although the Vat and Tsh homologues have been identified as virulence factors of ExPEC, their contributions to bloodstream infection are still unclear. In this study, VatPU-1 and TshPU-1 were verified to interact with the hemoglobin (a well-known mucin-like glycoprotein in red blood cell), degrade the mucins of host respiratory tract, and cleave the CD43 (a major cell surface component sharing similar O-glycosylated modifications with other glycoprotein expressed on leukocytes), suggesting that these two SPATEs have the common activity to cleave a broad array of mucin-like O-glycoproteins. These cleavages significantly impaired the chemotaxis and transmigration of leukocytes, and then inhibited the activation of diverse immune responses coordinately, especially downregulated the leukocytic and inflammatory activation during bloodstream infection, thus might mediate the evasion of ExPEC from immune clearance of blood leukocytes. Taken together, these two SPATEs play critical roles to cause a heavy bacterial load within bloodstream via immunomodulation of leukocytes, which provides a more comprehensive understanding how ExPEC colonize within host bloodstream and cause severe sepsis.
摘要：
肠外致病性大肠杆菌（ExPEC）是广泛的鸟类和哺乳动物血液感染的主要原因之一，因此对公众健康构成了巨大威胁，而其引起脓毒症的潜在机制尚不完全清楚。在这里，我们报道了一种高毒力的ExPEC菌株PU-1，它具有在宿主血流中定殖的强大能力，同时诱导低水平的白细胞活化。肠杆菌科（SPATEs）的两个丝氨酸蛋白酶自转运蛋白，发现VatPU-1和TshPU-1在菌株PU-1的紧急血液感染中起关键作用。尽管Vat和Tsh同系物已被确定为ExPEC的毒力因子，他们对血流感染的贡献仍不清楚.在这项研究中,验证了VatPU-1和TshPU-1与血红蛋白（红细胞中一种众所周知的粘蛋白样糖蛋白）相互作用，降解宿主呼吸道的粘蛋白，并切割CD43（与白细胞上表达的其他糖蛋白共享相似的O-糖基化修饰的主要细胞表面成分），这表明这两种SPATE具有切割大量粘蛋白样O-糖蛋白的共同活性。这些分裂显著损害了白细胞的趋化性和迁移，然后协调地抑制多种免疫反应的激活，尤其是在血流感染期间下调白细胞和炎症激活，因此，可能介导ExPEC逃避血液白细胞的免疫清除。一起来看,这两种SPATEs发挥关键作用，通过白细胞的免疫调节在血流中引起重的细菌负荷，这提供了更全面的了解ExPEC如何在宿主血液中定植并导致严重的败血症。
