Rapid paracellular transmigration of Campylobacter jejuni across polarized epithelial cells without affecting TER: role of proteolytic-active HtrA cleaving E-cadherin but not fibronectin.
Rapid paracellular transmigration of Campylobacter jejuni across polarized epithelial cells without affecting TER: role of proteolytic-active HtrA cleaving E-cadherin but not fibronectin.
复制标题
弯曲杆菌的弯曲杆菌在极化上皮细胞上的快速细胞跨移民不影响TER：蛋白水解活性HTRA裂解E-钙粘蛋白的作用，而不是纤连蛋白。
DOI：
10.1186/1757-4749-4-3
复制
发表时间：
2012-04-25
期刊：
影响因子：
4.2
通讯作者：
Backert S
中科院分区：
文献类型：
--
作者：
Boehm M;Hoy B;Rohde M;Tegtmeyer N;Bæk KT;Oyarzabal OA;Brøndsted L;Wessler S;Backert S
空肠弯曲菌是世界范围内引起食源性疾病的重要病原菌之一。通过肠上皮屏障和宿主细胞进入C。空肠被认为是肠组织损伤的主要原因，但这一过程中涉及的分子机制以及主要的细菌和宿主细胞因子仍广泛不清楚。本研究对C. jejuni作为一种分泌型毒力因子，具有重要的蛋白水解功能。感染研究和体外切割试验表明，C。空肠的HtrA触发非极化INT-407和极化MKN-28上皮细胞的细胞外E-钙粘蛋白NTF结构域（90 kDa）的脱落，但纤连蛋白不像H. pylori的HtrA。在C.空肠或表达蛋白酶缺陷的S197 A点突变体不会导致鞭毛的丧失或细菌运动性的降低，但会导致E-钙粘蛋白切割和细菌穿过极化的MKN-28细胞层的迁移的严重缺陷。与其他高度侵袭性的病原体不同，野生型C。空肠是高效的并且在感染后几分钟内完成。有趣的是，C.空肠杆菌以有限的方式发生，并且移行需要完整的鞭毛以及HtrA蛋白酶活性，但不降低跨上皮电阻（TER），如沙门氏菌、志贺氏菌、李斯特菌或奈瑟氏菌所见。这些结果表明，HtrA介导的E-cadherin切割参与了C.空肠通过非常特异的机制，使用细胞旁途径到达基底外侧表面，但不切割细胞进入所必需的纤连蛋白受体。
Campylobacter jejuni is one of the most important bacterial pathogens causing food-borne illness worldwide. Crossing the intestinal epithelial barrier and host cell entry by C. jejuni is considered the primary reason of damage to the intestinal tissue, but the molecular mechanisms as well as major bacterial and host cell factors involved in this process are still widely unclear. In the present study, we characterized the serine protease HtrA (high-temperature requirement A) of C. jejuni as a secreted virulence factor with important proteolytic functions. Infection studies and in vitro cleavage assays showed that C. jejuni’s HtrA triggers shedding of the extracellular E-cadherin NTF domain (90 kDa) of non-polarised INT-407 and polarized MKN-28 epithelial cells, but fibronectin was not cleaved as seen for H. pylori’s HtrA. Deletion of the htrA gene in C. jejuni or expression of a protease-deficient S197A point mutant did not lead to loss of flagella or reduced bacterial motility, but led to severe defects in E-cadherin cleavage and transmigration of the bacteria across polarized MKN-28 cell layers. Unlike other highly invasive pathogens, transmigration across polarized cells by wild-type C. jejuni is highly efficient and is achieved within a few minutes of infection. Interestingly, E-cadherin cleavage by C. jejuni occurs in a limited fashion and transmigration required the intact flagella as well as HtrA protease activity, but does not reduce transepithelial electrical resistance (TER) as seen with Salmonella, Shigella, Listeria or Neisseria. These results suggest that HtrA-mediated E-cadherin cleavage is involved in rapid crossing of the epithelial barrier by C. jejuni via a very specific mechanism using the paracellular route to reach basolateral surfaces, but does not cleave the fibronectin receptor which is necessary for cell entry.
登录
查看更多内容
影响因子：
3.1
作者：
Chen, Ming L.;Ge, Zhongming;Schauer, David B.
通讯作者：
Schauer, David B.
HTRA伴侣的活性有助于弯曲杆菌空肠的宿主细胞结合。
影响因子：
4.2
作者：
Bæk KT;Vegge CS;Brøndsted L
通讯作者：
Brøndsted L
影响因子：
7.7
作者：
Hoy, Benjamin;Loewer, Martin;Wessler, Silja
通讯作者：
Wessler, Silja
影响因子：
4.2
作者：
Kalischuk LD;Inglis GD;Buret AG
通讯作者：
Buret AG
弯曲杆菌空肠的宿主上皮细胞侵袭：触发或拉链机制？
影响因子：
5.7
作者：
O Cróinín T;Backert S
通讯作者：
Backert S