Department of Microbial Diseases, UCL Eastman Dental Institute, University College London, London, United Kingdom.
PLoS One. 2011;6(8):e23014. doi: 10.1371/journal.pone.0023014. Epub 2011 Aug 18.
Clostridium difficile is the leading cause of hospital-associated diarrhoea in the US and Europe. Recently the incidence of C. difficile-associated disease has risen dramatically and concomitantly with the emergence of 'hypervirulent' strains associated with more severe disease and increased mortality. C. difficile contains numerous mobile genetic elements, resulting in the potential for a highly plastic genome. In the first sequenced strain, 630, there is one proven conjugative transposon (CTn), Tn5397, and six putative CTns (CTn1, CTn2 and CTn4-7), of which, CTn4 and CTn5 were capable of excision. In the second sequenced strain, R20291, two further CTns were described.
CTn1, CTn2 CTn4, CTn5 and CTn7 were shown to excise from the genome of strain 630 and transfer to strain CD37. A putative CTn from R20291, misleadingly termed a phage island previously, was shown to excise and to contain three putative mobilisable transposons, one of which was capable of excision. In silico probing of C. difficile genome sequences with recombinase gene fragments identified new putative conjugative and mobilisable transposons related to the elements in strains 630 and R20291. CTn5-like elements were described occupying different insertion sites in different strains, CTn1-like elements that have lost the ability to excise in some ribotype 027 strains were described and one strain was shown to contain CTn5-like and CTn7-like elements arranged in tandem. Additionally, using bioinformatics, we updated previous gene annotations and predicted novel functions for the accessory gene products on these new elements.
The genomes of the C. difficile strains examined contain highly related CTns suggesting recent horizontal gene transfer. Several elements were capable of excision and conjugative transfer. The presence of antibiotic resistance genes and genes predicted to promote adaptation to the intestinal environment suggests that CTns play a role in the interaction of C. difficile with its human host.
艰难梭菌是美国和欧洲医院相关腹泻的主要原因。最近，艰难梭菌相关性疾病的发病率急剧上升，同时出现了与更严重疾病和更高死亡率相关的“高毒力”菌株。艰难梭菌含有许多移动遗传元件，导致其基因组具有高度可塑性。在第一个测序的菌株 630 中，有一个已证实的可接合转座子（CTn），Tn5397，和六个假定的 CTn（CTn1、CTn2 和 CTn4-7），其中 CTn4 和 CTn5 能够切除。在第二个测序的菌株 R20291 中，描述了另外两个 CTn。
CTn1、CTn2、CTn4、CTn5 和 CTn7 被证明从 630 株的基因组中切除，并转移到 CD37 株。先前被错误地称为噬菌体岛的来自 R20291 的一个假定 CTn，被证明能够切除，并包含三个假定的可移动转座子，其中一个能够切除。用重组酶基因片段对艰难梭菌基因组序列进行计算机探测，鉴定出与 630 株和 R20291 株相关的新的假定可接合和可移动转座子。描述了不同菌株中占据不同插入位点的 CTn5 样元件，描述了一些 027 型核糖体中丧失切除能力的 CTn1 样元件，并且一个菌株被证明含有串联排列的 CTn5 样和 CTn7 样元件。此外，我们利用生物信息学更新了以前的基因注释，并预测了这些新元件上辅助基因产物的新功能。
所检查的艰难梭菌菌株的基因组包含高度相关的 CTn，表明最近发生了水平基因转移。几个元件能够切除和接合转移。抗生素耐药基因和预测促进适应肠道环境的基因的存在表明，CTn 在艰难梭菌与宿主的相互作用中发挥作用。
