Cytolethal Distending Toxin Type I and Type IV Genes Are Framed with Lambdoid Prophage Genes in Extraintestinal Pathogenic Escherichia coli

Cytolethal Distending Toxin Type I and Type IV Genes Are Framed with Lambdoid Prophage Genes in Extraintestinal Pathogenic Escherichia coli
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DOI:
10.1128/iai.00962-08
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发表时间:
2009-01-01
影响因子:
3.1
通讯作者:
Oswald, Eric
Oswald, Eric
中科院分区:
医学2区
文献类型:
--
作者:
Toth, Istvan;Nougayrede, Jean-Philippe;Oswald, Eric

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在大肠杆菌中已鉴定出五种类型的细胞致死膨胀毒素(CDT-I 至 CDT-V)。在本研究中,我们对属于 O75 血清群的猪肠外致病性大肠杆菌 (ExPEC) 菌株的 cdt-IV 操纵子和侧翼区域进行了克隆和测序。我们证实,与其他 CDT 类似,CDT-IV 诱导宿主组蛋白 H2AX(DNA 双链断裂的敏感标记)磷酸化,并在 G(2)-M 转变时阻断 HeLa 细胞周期。 cdt-IV 基因由人字形原噬菌体基因构建。我们对人 ExPEC O18:K1:H7 菌株的 cdt-I 操纵子和侧翼区域进行了克隆和测序,并观察到 ​​cdt-I 基因的侧翼也有羔羊状原噬菌体基因。 PCR研究表明,编码推定蛋白酶的基因总是与cdtC-IV基因相关,但与产生CDT-I、CDT-III和CDT-V的菌株中的cdtC基因不相关。我们的结果表明,cdt-I 和 cdt-IV 基因可能是通过噬菌体转导从共同祖先获得的,并在其细菌宿主中进化。溶原性噬菌体有可能携带非必需的“货物”基因或“白痴”基因,因此在 ExPEC 内遗传多样性的产生中发挥着至关重要的作用。
Five types of cytolethal distending toxin (CDT-I to CDT-V) have been identified in Escherichia coli. In the present study we cloned and sequenced the cdt-IV operon and flanking region from a porcine extraintestinal pathogenic E. coli (ExPEC) strain belonging to serogroup O75. We confirmed that similar to other CDTs, CDT-IV induced phosphorylation of host histone H2AX, a sensitive marker of DNA double-strand breaks, and blocked the HeLa cell cycle at the G(2)-M transition. The cdt-IV genes were framed by lambdoid prophage genes. We cloned and sequenced the cdt-I operon and flanking regions from a human ExPEC O18:K1:H7 strain and observed that cdt-I genes were also flanked by lambdoid prophage genes. PCR studies indicated that a gene coding for a putative protease was always associated with the cdtC-IV gene but was not associated with cdtC genes in strains producing CDT-I, CDT-III, and CDT-V. Our results suggest that the cdt-I and cdt-IV genes might have been acquired from a common ancestor by phage transduction and evolved in their bacterial hosts. The lysogenic bacteriophages have the potential to carry nonessential "cargo" genes or "morons" and therefore play a crucial role in the generation of genetic diversity within ExPEC.