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

The bla_KPC-2 gene encodes a carbapenemase that hydrolyses almost all β-lactams, including carbapenems. The rapid emergence and international spread of this gene in Enterobacteriaceae seriously limits clinical treatment, posing an alarming threat for public health. Transposable elements often play a role in the dissemination of bla_KPC-2 gene, such as Tn4401, a proved transposon in Europe, USA etc. In eastern China, the bla_KPC-2 gene is frequently associated with several novel structures of Tn1721, but their transposition ability and mechanism remain unclear. Here we experimentally demonstrated that Tn1721-like transposons are capable of transferring the bla_KPC-2, both internal and external to the Tn1721 element, from one strain to another, and that distinct transposon structures exhibited different movement patterns and transposition frequencies. This process did not involve homologous recombination. Moreover, 5-bp duplication of target site, a characterized signature of transposition evens in Tn3-family, was confirmed. Tn1721-like transposons were found preferentially to insert into a 5-bp region exhibiting a degenerated degree of AT-rich from both sides to the middle gradually, and immediately flanked by GC-rich positions. The observation in clinical isolates, including the prevalence of Tn1721-like transposons, diverse sequences flanking the transposons and 5-bp duplication of target site, etc. also sustained our experiment results. This study gives evidences of the functional role of Tn1721-like transposons in transferring bla_KPC-2 gene firstly, and provides a new sight for the transposable element and the dissemination of antibiotic resistance in Enterobacteriaceae.

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