Translocation of Carbapenemase Gene blaKPC-2 both Internal and External to Transposons Occurs via Novel Structures of Tn1721 and Exhibits Distinct Movement Patterns
Translocation of Carbapenemase Gene blaKPC-2 both Internal and External to Transposons Occurs via Novel Structures of Tn1721 and Exhibits Distinct Movement Patterns
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碳青霉烯酶基因 blaKPC-2 通过 Tn1721 的新颖结构在内部和外部易位至转座子，并表现出独特的运动模式
DOI：
10.1128/aac.01151-17
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发表时间：
2017-10-01
影响因子：
4.9
通讯作者：
Jiang, Xiaofei
中科院分区：
文献类型：
--
作者：
Tang, Yu;Li, Gang;Jiang, Xiaofei
bla(KPC-2) 基因编码碳青霉烯酶，可水解几乎所有 β-内酰胺，包括碳青霉烯类。该基因在肠杆菌科细菌中的迅速出现和国际传播严重限制了临床治疗，对公众健康构成了惊人的威胁。转座因子，例如 Tn4401，一种在欧洲、美国和其他地方已被证实的转座子，通常在 blaKpc.. 基因的传播中发挥作用。在中国东部，bla(KPC-2)基因经常与Tn1721的几种新结构相关，但它们的转座能力和运动机制仍不清楚。在这里，我们通过实验证明，Tn1721 样转座子能够将 bla(KPC-2) 从一种菌株内部和外部转移到 Tn1721 元件到另一种菌株，并且不同的转座子结构表现出不同的运动模式和转座频率。该过程不涉及同源重组。此外，还确认了目标位点的 5 bp 重复，这是 Tn3 家族中转座事件的特征。研究发现，Tn1721 样转座子优先插入 5 bp 区域，该区域从两侧到中间逐渐表现出 AT 丰富区域的退化程度，并且紧邻 GC 丰富区域。在临床分离株中观察到的转座子侧翼的不同序列和靶位点的 5 bp 重复，以及 Tn/721 样转座子的普遍性，也支持了我们的实验结果。这项研究首先提供了 Tn 1721 样转座子在转移 biaKpc_, 基因中的功能作用的证据，并为转座元件和肠杆菌科抗生素耐药性的传播提供了新的视角。
The bla(KPC-2) gene encodes a carbapenemase that hydrolyzes almost all beta-lactams, including carbapenems. The rapid emergence and international spread of this gene in Enterobacteriaceae seriously limit clinical treatment, posing an alarming threat for public health. Transposable elements, such as Tn4401, a proven transposon in Europe, the United States, and elsewhere, often playa role in the dissemination of the blaKpc.., gene. In eastern China, the bla(KPC-2) gene is frequently associated with several novel structures of Tn1721, but their transposition ability and mechanism of movement remain unclear. Here, we experimentally demonstrate that Tn1721-like transposons are capable of transferring bla(KPC-2) both internal and external to the Tn1721 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 Tn3 family, was confirmed. Tn1721-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/721-like transposons, also sustained our experimental results. This study first gives evidence about the functional role of Tn 1721-like transposons in transferring the biaKpc_, gene and provides new sight into the transposable element and the dissemination of antibiotic resistance in Enterobacteriaceae.