Horizontal gene transfer converts non-toxigenic Clostridium difficile strains into toxin producers

Horizontal gene transfer converts non-toxigenic Clostridium difficile strains into toxin producers
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DOI:
10.1038/ncomms3601
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发表时间:
2013-10-01
影响因子:
16.6
通讯作者:
Mullany, Peter
Mullany, Peter
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Brouwer, Michael S. M.;Roberts, Adam P.;Mullany, Peter

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艰难梭菌是一种主要的医院病原体,也是抗生素相关性腹泻的主要病原体。该生物体产生两种强效毒素A和B,这是其主要毒力因子。这些是染色体编码的一个区域称为致病性基因座(PaLoc),其中也含有调控基因,是不存在的非致病性菌株。在这里,我们表明,PaLoc可以从产毒素菌株,630德尔塔,转移到三个不同的核糖体型的非转基因菌株。细胞毒性试验表明,其中一个接合子产生的毒素B与供体菌株的水平相似,证明了一个产毒C。艰难梭菌菌株能够通过水平基因转移将非产毒菌株转化为产毒素菌株。这对C.艰难梭菌感染,因为非致病性菌株正在临床试验中作为治疗进行测试。
Clostridium difficile is a major nosocomial pathogen and the main causative agent of antibioticassociated diarrhoea. The organism produces two potent toxins, A and B, which are its major virulence factors. These are chromosomally encoded on a region termed the pathogenicity locus (PaLoc), which also contains regulatory genes, and is absent in non-toxigenic strains. Here we show that the PaLoc can be transferred from the toxin-producing strain, 630 Delta erm, to three non-toxigenic strains of different ribotypes. One of the transconjugants is shown by cytotoxicity assay to produce toxin B at a similar level to the donor strain, demonstrating that a toxigenic C. difficile strain is capable of converting a non-toxigenic strain to a toxin producer by horizontal gene transfer. This has implications for the treatment of C. difficile infections, as non-toxigenic strains are being tested as treatments in clinical trials.