Ismaili A, McWhirter E, Handelsman M Y, Brunton J L, Sherman P M
Research Institute, The Hospital for Sick Children, Department of Medical Genetics, University of Toronto, Ontario, Canada.
Infect Immun. 1998 Apr;66(4):1688-96. doi: 10.1128/IAI.66.4.1688-1696.1998.
Shiga toxin-producing Escherichia coli (STEC) O157:H7 is an attaching and effacing pathogen that causes hemorrhagic colitis and the hemolytic-uremic syndrome. Although this organism causes adhesion pedestals, the cellular signals responsible for the formation of these lesions have not been clearly defined. We have shown previously that STEC O157:H7 does not induce detectable tyrosine phosphorylation of host cell proteins upon binding to eukaryotic cells and is not internalized into nonphagocytic epithelial cells. In the present study, tyrosine-phosphorylated proteins were detected under adherent STEC O157:H7 when coincubated with the non-intimately adhering, intimin-deficient, enteropathogenic E. coli (EPEC) strain CVD206. The ability to be internalized into epithelial cells was also conferred on STEC O157:H7 when coincubated with CVD206 ([158 +/- 21] % of control). Neither the ability to rearrange phosphotyrosine proteins nor that to be internalized into epithelial cells was evident following coincubation with another STEC O157:H7 strain or with the nonsignaling espB mutant of EPEC. E. coli JM101(pMH34/pSSS1C), which overproduces surface-localized O157 intimin, also rearranged tyrosine-phosphorylated and cytoskeletal proteins when coincubated with CVD206. In contrast, JM101 (pMH34/pSSS1C) demonstrated rearrangement of cytoskeletal proteins, but not tyrosine-phosphorylated proteins, when coincubated with intimin-deficient STEC (strains CL8KO1 and CL15). These findings indicate that STEC O157:H7 forms adhesion pedestals by mechanisms that are distinct from those in attaching and effacing EPEC. Taken together, these findings point to diverging signal transduction responses to infection with attaching and effacing bacterial enteropathogens.
产志贺毒素大肠杆菌(STEC)O157:H7是一种黏附并破坏细胞的病原体,可引起出血性结肠炎和溶血尿毒综合征。尽管这种微生物会导致黏附基座的形成,但负责这些损伤形成的细胞信号尚未明确界定。我们之前已经表明,STEC O157:H7与真核细胞结合后不会诱导宿主细胞蛋白发生可检测到的酪氨酸磷酸化,也不会内化到非吞噬性上皮细胞中。在本研究中,当与非紧密黏附、缺乏紧密黏附素的肠致病性大肠杆菌(EPEC)菌株CVD206共同孵育时,在黏附的STEC O157:H7下检测到了酪氨酸磷酸化蛋白。当与CVD206共同孵育时,STEC O157:H7也获得了内化到上皮细胞中的能力(为对照的[158±21]%)。与另一种STEC O157:H7菌株或EPEC的无信号espB突变体共同孵育后,既没有磷酸酪氨酸蛋白重排的能力,也没有内化到上皮细胞中的能力。过量表达表面定位的O157紧密黏附素的大肠杆菌JM101(pMH34/pSSS1C)与CVD206共同孵育时,也会重排酪氨酸磷酸化和细胞骨架蛋白。相比之下,JM101(pMH34/pSSS1C)与缺乏紧密黏附素的STEC(CL8KO1和CL15菌株)共同孵育时,表现出细胞骨架蛋白的重排,但没有酪氨酸磷酸化蛋白的重排。这些发现表明,STEC O157:H7通过与黏附并破坏细胞的EPEC不同的机制形成黏附基座。综上所述,这些发现表明对黏附并破坏细胞的细菌性肠道病原体感染的信号转导反应存在差异。