Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Laboratory Medicine, Jinshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Antimicrob Agents Chemother. 2017 Sep 22;61(10). doi: 10.1128/AAC.01151-17. Print 2017 Oct.
The gene encodes a carbapenemase that hydrolyzes almost all β-lactams, including carbapenems. The rapid emergence and international spread of this gene in seriously limit clinical treatment, posing an alarming threat for public health. Transposable elements, such as Tn, a proven transposon in Europe, the United States, and elsewhere, often play a role in the dissemination of the gene. In eastern China, the gene is frequently associated with several novel structures of Tn, but their transposition ability and mechanism of movement remain unclear. Here, we experimentally demonstrate that Tn-like transposons are capable of transferring both internal and external to the Tn element from one strain to another and that distinct transposon structures exhibit different movement patterns and transposition frequencies. This process did not involve homologous recombination. Moreover, a 5-bp duplication of the target site, a characterized signature of transposition events in the Tn family, was confirmed. Tn-like transposons were found to insert preferentially into a 5-bp region that gradually exhibits a degenerated degree of AT-rich regions from both sides to the middle and that is immediately flanked by GC-rich regions. The observation in clinical isolates of diverse sequences flanking the transposons and a 5-bp duplication of the target site, as well as the prevalence of Tn-like transposons, also sustained our experimental results. This study first gives evidence about the functional role of Tn-like transposons in transferring the gene and provides new sight into the transposable element and the dissemination of antibiotic resistance in .
该基因编码一种碳青霉烯酶,几乎能水解所有β-内酰胺类抗生素,包括碳青霉烯类抗生素。这种基因在短时间内迅速出现并在国际上传播,严重限制了临床治疗,对公共健康构成了严重威胁。转座子,如 Tn,在欧洲、美国和其他地方已被证实是一种可转移因子,在该基因的传播中经常发挥作用。在中国东部,该基因经常与几种新型 Tn 结构有关,但它们的转座能力和运动机制尚不清楚。在这里,我们通过实验证明,Tn 样转座子能够将 基因内部和外部转移到 Tn 元件上,并从一个菌株转移到另一个菌株,不同的转座子结构表现出不同的运动模式和转座频率。这个过程不涉及同源重组。此外,还证实了 Tn 家族中转座事件的特征性标志——靶位点的 5 个碱基对重复。Tn 样转座子优先插入靶位点的 5 个碱基对重复区域,该区域从两侧到中间逐渐表现出退化的 AT 丰富度,两侧立即被 GC 丰富度所包围。转座子侧翼不同序列的临床分离株以及靶位点的 5 个碱基对重复的观察结果,以及 Tn 样转座子的普遍性,也支持了我们的实验结果。本研究首次证明了 Tn 样转座子在转移 基因方面的功能作用,并为转座子和抗生素耐药性在 中的传播提供了新的视角。