A diffusible cytotoxin of Haemophilus ducreyi
A diffusible cytotoxin of Haemophilus ducreyi
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DOI：
10.1073/pnas.94.8.4056
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
Hansen, EJ
中科院分区：
文献类型：
--
作者：
Cope, LD;Lumbley, S;Hansen, EJ
关于杜克雷嗜血杆菌在生殖器溃疡产生中所采用的毒力机制知之甚少。这种革兰氏阴性细菌先前已被证明产生杀死HeLa和HEp-2细胞的可溶性细胞毒性活性。我们现在已经确定了一个由三个H组成的簇。ducreyi基因编码这种细胞毒活性。这些基因编码的预测的蛋白质是最相似的大肠杆菌cdtABC基因，包括这种肠道病原体的细胞致死膨胀毒素（CDT）的产品。十二点十一分。ducreyi菌株显示具有该基因簇，并且来自这些菌株的培养物上清液容易杀死HeLa细胞。从单株H.缺乏这些基因的ducreyi无法杀死HeLa细胞。当H.将ducreyi cdtABC基因簇克隆到E. coli，重组大肠杆菌的培养上清中，用琼脂糖凝胶电泳法测定了重组大肠杆菌的蛋白质含量。coli克隆杀死HeLa细胞。一种单克隆抗体中和了H. ducreyi与H. ducreyi cdtC基因产物。这种可溶性H. ducreyi细胞毒素可能在软下疳特征性溃疡性病变的发展或持续中起作用。
Little is known about the virulence mechanisms employed by Haemophilus ducreyi in the production of genital ulcers. This Gram-negative bacterium previously has been shown to produce a soluble cytotoxic activity that kills HeLa and HEp-2 cells. We have now identified a cluster of three H. ducreyi genes that encode this cytotoxic activity. The predicted proteins encoded by these genes are most similar to the products of the Escherichia coli cdtABC genes that comprise the cytolethal distending toxin (CDT) of this enteric pathogen. Eleven of 12 H. ducreyi strains were shown to possess this gene cluster and culture supernatants from these strains readily killed HeLa cells. The culture supernatant from a single strain of H. ducreyi that lacked these genes was unable to kill HeLa cells. When the H. ducreyi cdtABC gene cluster was cloned into E. coli, culture supernatant from the recombinant E. coli clone killed HeLa cells. A monoclonal antibody that neutralized this soluble cytotoxic activity of H. ducreyi was shown to bind to the H. ducreyi cdtC gene product. This soluble H. ducreyi cytotoxin may play a role in the development or persistence of the ulcerative lesions characteristic of chancroid.