Translocation of Carbapenemase Gene blaKPC-2 both Internal and External to Transposons Occurs via Novel Structures of Tn1721 and Exhibits Distinct Movement Patterns.

The blaKPC-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 Tn4401, a proven transposon in Europe, the United States, and elsewhere, often play a role in the dissemination of the blaKPC-2 gene. In eastern China, the blaKPC-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 blaKPC-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 Tn1721-like transposons, also sustained our experimental results. This study first gives evidence about the functional role of Tn1721-like transposons in transferring the blaKPC-2 gene and provides new sight into the transposable element and the dissemination of antibiotic resistance in Enterobacteriaceae.