Colibactin: More Than a New Bacterial Toxin.

Colibactin: More Than a New Bacterial Toxin.
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DOI:
10.3390/toxins10040151
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发表时间:
2018-04-10
期刊:
影响因子:
4.2
通讯作者:
Dalmasso G
Dalmasso G
中科院分区:
医学2区
文献类型:
--
作者:
Faïs T;Delmas J;Barnich N;Bonnet R;Dalmasso G

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环调节素是干扰真核细胞周期的细菌毒素。由pks基因组岛合成的一种名为大肠杆菌蛋白(colibactin)的新型环调节蛋白于2006年被发现。尽管做了许多努力,大肠杆菌蛋白尚未被纯化,其结构仍然难以捉摸。有趣的是,pks岛存在于肠杆菌科的成员(主要是大肠杆菌和肺炎克雷伯菌)中,这些成员来自不同的来源,包括肠道微生物群、败血症、新生儿脑膜炎和尿路感染。产生大肠杆菌素的细菌诱导真核细胞的染色体不稳定和DNA损伤,从而导致上皮细胞衰老和免疫细胞凋亡。pks岛主要存在于B2系统群大肠杆菌菌株中,其中包括肠外致病性大肠杆菌菌株,在结直肠癌活检中pks岛较多。此外,pks大肠杆菌增加了多种结直肠癌小鼠模型中的肿瘤数量。因此,大肠杆菌蛋白可能对人类健康产生重大影响。本文将对大肠杆菌蛋白的生物学作用、pks岛的分布以及目前对其合成和结构的了解进行综述。
Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle. A new cyclomodulin called colibactin, which is synthetized by the pks genomic island, was discovered in 2006. Despite many efforts, colibactin has not yet been purified, and its structure remains elusive. Interestingly, the pks island is found in members of the family Enterobacteriaceae (mainly Escherichia coli and Klebsiella pneumoniae) isolated from different origins, including from intestinal microbiota, septicaemia, newborn meningitis, and urinary tract infections. Colibactin-producing bacteria induce chromosomal instability and DNA damage in eukaryotic cells, which leads to senescence of epithelial cells and apoptosis of immune cells. The pks island is mainly observed in B2 phylogroup E. coli strains, which include extra-intestinal pathogenic E. coli strains, and pks E. coli are over-represented in biopsies isolated from colorectal cancer. In addition, pks E. coli bacteria increase the number of tumours in diverse colorectal cancer mouse models. Thus, colibactin could have a major impact on human health. In the present review, we will focus on the biological effects of colibactin, the distribution of the pks island, and summarize what is currently known about its synthesis and its structure.
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