Zychlinsky A, Prevost M C, Sansonetti P J
Unité de Pathogénie Microbienne Moléculaire, INSERM U199, Institut Pasteur, Paris, France.
Nature. 1992 Jul 9;358(6382):167-9. doi: 10.1038/358167a0.
The Gram-negative bacterial pathogen Shigella flexneri causes dysentery by invading the human colonic mucosa. Bacteria are phagocytosed by enterocytes, escape from the phagosome into the cytoplasm and spread to adjacent cells. After crossing the epithelium, Shigella reaches the lamina propria of intestinal villi, the first line of defence. This tissue is densely populated with phagocytes that are killed in great numbers, resulting in abscesses. The genes required for cell invasion and macrophage killing are located on a 220-kilobase plasmid. We report here on the mechanism of cytotoxicity used by S. flexneri to kill macrophages. Each of four different strains was tested for its capacity to induce cell death. An invasive strain induced programmed cell death (apoptosis), whereas its non-invasive, plasmidcured isogenic strain was not toxic; neither was a mutant in ipa B (ref. 10) (invasion protein antigen), a gene necessary for entry. A non-invasive strain expressing the haemolysin operon of Escherichia coli induced accidental cell death (necrosis), demonstrating that other bacterial cytotoxic mechanisms do not lead to apoptosis. This is the first evidence that an invasive bacterial pathogen can induce suicide in its host cells.
革兰氏阴性细菌病原体福氏志贺菌通过侵入人结肠黏膜引发痢疾。细菌被肠上皮细胞吞噬，从吞噬体逃逸到细胞质中并扩散到相邻细胞。穿过上皮细胞后，志贺菌到达肠绒毛的固有层，这是第一道防线。该组织中密集分布着大量被杀死的吞噬细胞，从而形成脓肿。细胞侵袭和巨噬细胞杀伤所需的基因位于一个220千碱基的质粒上。我们在此报告福氏志贺菌用于杀死巨噬细胞的细胞毒性机制。对四种不同菌株诱导细胞死亡的能力进行了测试。一株侵袭性菌株诱导程序性细胞死亡（凋亡），而其非侵袭性、质粒消除的同基因菌株无毒；参与入侵的必需基因ipa B（参考文献10）的突变体也无毒。一株表达大肠杆菌溶血素操纵子的非侵袭性菌株诱导意外细胞死亡（坏死），表明其他细菌细胞毒性机制不会导致凋亡。这是侵袭性细菌病原体可诱导宿主细胞自杀的首个证据。
