Translocation of Carbapenemase Gene bla KPC-2 both Internal and External to Transposons Occurs via Novel Structures of Tn 1721 and Exhibits Distinct Movement Patterns

The bla KPC-2 gene encodes a carbapenemase that hydrolyzes almost all β-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 Tn 4401 , a proven transposon in Europe, the United States, and elsewhere, often play a role in the dissemination of the bla KPC-2 gene. In eastern China, the bla KPC-2 gene is frequently associated with several novel structures of Tn 1721 , but their transposition ability and mechanism of movement remain unclear. Here, we experimentally demonstrate that Tn 1721 -like transposons are capable of transferring bla KPC-2 both internal and external to the Tn 1721 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 3 family, was confirmed. Tn 1721 -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 1721 -like transposons, also sustained our experimental results. This study first gives evidence about the functional role of Tn 1721 -like transposons in transferring the bla KPC-2 gene and provides new sight into the transposable element and the dissemination of antibiotic resistance in Enterobacteriaceae .