Chromosomal Integration of Huge and Complex blaNDM-Carrying Genetic Elements in Enterobacteriaceae

• Published in: Frontiers in cellular and infection microbiology 2021-06, Vol.11
• Main Authors: Luo, Xinhua, Yin, Zhe, Zeng, Lijun, Hu, Lingfei, Jiang, Xiaoyuan, Jing, Ying, Chen, Fangzhou, Wang, Dongguo, Song, Yajun, Yang, Huiying, Zhou, Dongsheng
• Format: Article
• Language: English
• Subjects: blaNDM; chromosomal integration; Enterobacteriaceae; mobile genetic elements; multidrug resistance
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2021.690799

In this study, a detailed genetic dissection of the huge and complex bla NDM -carrying genetic elements and their related mobile genetic elements was performed in Enterobacteriaceae. An extensive comparison was applied to 12 chromosomal genetic elements, including six sequenced in this study and the other six from GenBank. These 12 genetic elements were divided into five groups: a novel IME Tn 6588 ; two related IMEs Tn 6523 (SGI1) and Tn 6589 ; four related ICEs Tn 6512 (R391), Tn 6575 (ICE Pvu ChnBC22), Tn 6576 , and Tn 6577 ; Tn 7 and its derivatives Tn 6726 and 40.7-kb Tn 7 -related element; and two related IMEs Tn 6591 (GI sul2 ) and Tn 6590 . At least 51 resistance genes, involved in resistance to 18 different categories of antibiotics and heavy metals, were found in these 12 genetic elements. Notably, Tn 6576 carried another ICE Tn 6582 . In particular, the six bla NDM -carrying genetic elements Tn 6588 , Tn 6589 , Tn 6575 , Tn 6576 , Tn 6726 , and 40.7-kb Tn 7 -related element contained large accessory multidrug resistance (MDR) regions, each of which had a very complex mosaic structure that comprised intact or residual mobile genetic elements including insertion sequences, unit or composite transposons, integrons, and putative resistance units. Core bla NDM genetic environments manifested as four different Tn 125 derivatives and, notably, two or more copies of relevant Tn 125 derivatives were found in each of Tn 6576 , Tn 6588 , Tn 6589 , and 40.7-kb Tn 7 -related element. The huge and complex bla NDM -carrying genetic elements were assembled from complex transposition and homolog recombination. Firstly identified were eight novel mobile elements, including three ICEs Tn 6576 , Tn 6577 , and Tn 6582 , two IMEs, Tn 6588 and Tn 6589 , two composite transposons Tn 6580a and Tn 6580b , and one integron In1718.