Whitehouse C A, Balbo P B, Pesci E C, Cottle D L, Mirabito P M, Pickett C L
Department of Microbiology and Immunology, College of Medicine, Chandler Medical Center, University of Kentucky, Lexington 40536-0084, USA.
Infect Immun. 1998 May;66(5):1934-40. doi: 10.1128/IAI.66.5.1934-1940.1998.
Cytolethal distending toxin (CDT) from the diarrheagenic bacterium Campylobacter jejuni was shown to cause a rapid and specific cell cycle arrest in HeLa and Caco-2 cells. Within 24 h of treatment, CDT caused HeLa cells to arrest with a 4N DNA content, indicative of cells in G2 or early M phase. Immunofluorescence studies indicated that the arrested cells had not entered M phase, since no evidence of tubulin reorganization or chromatin condensation was visible. CDT treatment was also shown to cause HeLa cells to accumulate the inactive, tyrosine-phosphorylated form of CDC2. These results indicated that CDT treatment results in a failure to activate CDC2, which leads to cell cycle arrest in G2. This mechanism of action is novel for a bacterial toxin and provides a model for the generation of diarrheal disease by C. jejuni and other diarrheagenic bacteria that produce CDT.
空肠弯曲杆菌产生的细胞致死性膨胀毒素（CDT）被证明可使HeLa细胞和Caco-2细胞快速且特异性地发生细胞周期阻滞。在处理24小时内，CDT使HeLa细胞停滞于4N DNA含量水平，这表明细胞处于G2期或M期早期。免疫荧光研究表明，停滞的细胞尚未进入M期，因为未观察到微管蛋白重组或染色质凝聚的迹象。CDT处理还显示可使HeLa细胞积累无活性的酪氨酸磷酸化形式的CDC2。这些结果表明，CDT处理导致无法激活CDC2，从而导致细胞在G2期发生周期阻滞。这种作用机制对于细菌毒素而言是全新的，并为产CDT的空肠弯曲杆菌及其他致泻性细菌引发腹泻病提供了一个模型。
