State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan, China.
Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Jinan, China.
Int J Antimicrob Agents. 2017 Aug;50(2):242-246. doi: 10.1016/j.ijantimicag.2017.01.045. Epub 2017 Jun 8.
Integrative and conjugative elements (ICEs) are self-transmissible chromosomal mobile elements that play significant roles in the dissemination of antimicrobial resistance genes. Identification of the structures and functions of ICEs, particularly those in pathogens, improves understanding of the dissemination of antimicrobial resistance. This study identified new members of the sulfamethoxazole-trimethoprim (SXT)/R391 family of ICEs that could confer multi-drug resistance in the opportunistic pathogen Proteus mirabilis, characterized their genetic structures, and explored their evolutionary connection with other members of this family of ICEs. Three new members of the SXT/R391 family of ICEs were detected in six of 77 P. mirabilis strains isolated in China: ICEPmiChn2 (one strain), ICEPmiChn3 (one strain) and ICEPmiChn4 (three strains). All three new ICEs harbour antimicrobial resistance genes from diverse origins, suggesting their capability in acquiring foreign genes and serving as important carriers for antimicrobial resistance genes. Structural analysis showed that ICEPmiChn3 is a particularly interesting and unique ICE that has lost core genes involved in conjugation, and could not transfer to other cells via conjugation. This finding confirmed the key roles of these missing genes in conjugation. Further phylogenetic analysis suggested that ICEs in geographically close strains are also connected evolutionarily, and ICEPmiChn3 lost its conjugation cassette from a former mobile ICE. The identification and characterization of the three new members of the SXT/R391 family of ICEs in this work leads to suggestions of core ICE genes essential for conjugation, and extends understanding on the structures of ICEs, evolutionary relationships between ICEs, and the antimicrobial resistance mechanisms of P. mirabilis.
整合子-接合性元件（ICEs）是可自我转移的染色体移动元件，在抗生素耐药基因的传播中发挥着重要作用。鉴定 ICEs 的结构和功能，特别是在病原体中的 ICEs，有助于了解抗生素耐药性的传播。本研究鉴定了磺胺甲噁唑-甲氧苄啶（SXT）/R391 家族的新型 ICEs，它们能够赋予机会性病原体奇异变形杆菌的多药耐药性，对其遗传结构进行了特征描述，并探讨了它们与该家族其他 ICEs 的进化关系。在中国分离的 77 株奇异变形杆菌中，有 6 株（1 株）分离到 ICEPmiChn2、（1 株）分离到 ICEPmiChn3 和（3 株）分离到 ICEPmiChn4，这三个新的 SXT/R391 家族 ICE 均携带来自不同来源的抗生素耐药基因，表明它们有获取外来基因的能力，是抗生素耐药基因的重要载体。结构分析表明，ICEPmiChn3 是一种特别有趣和独特的 ICE，它失去了与接合有关的核心基因，不能通过接合转移到其他细胞。这一发现证实了这些缺失基因在接合中的关键作用。进一步的系统发育分析表明，地理位置相近的菌株中的 ICEs 在进化上也存在联系，而 ICEPmiChn3 的接合盒从前一个移动 ICE 中丢失。本研究鉴定和描述了 SXT/R391 家族的三个新型 ICE，提出了核心 ICE 基因对接合至关重要的假说，并扩展了对 ICEs 结构、ICEs 之间的进化关系以及奇异变形杆菌抗生素耐药机制的认识。
