Miniature inverted-repeat transposable elements mobilize diverse antibiotic resistance genes in Enterobacteriaceae

Miniature inverted-repeat transposable elements (MITEs) are nonautonomous mobile genetic elements (MGEs) that can be mobilized by transposases provided by the relevant autonomous MGEs. Composite transposon-like structures bounded by two MITE copies, designated MITE-COMPs, were previously shown to mobilize the intervening sequences. However, their association with antibiotic-resistance genes (ARGs) has not yet been systematically studied, and only a few MITE-COMP structures with ARGs have been reported to date. This study thus aimed to identify new MITE-COMP members containing ARGs in the genomic sequences of the clinically important bacterial family Enterobacteriaceae in public databases. MITE-COMPs were first searched for in the PLSDB database, focusing on small plasmids, using a self-against-self blastn approach. Then, newly and previously identified MITEs were searched for in the NCBI core nucleotide database to identify MITE-COMPs located on other replicons. Bioinformatics analyses identified multiple previously unreported MITE-COMP structures containing ARGs, which are bounded by directly or inversely oriented MITEs, including IS 101 , MITESen1, and a novel 244-bp MITE termed MITE244. All these MITEs seem to have originated from transposons of the Tn 3 family. MITE244 contains a putative cointegrate resolution site related to Tn 21 , and MITE244 copies in MITE-COMPs were predominantly found in inverse orientation. The ARGs embedded in newly identified MITE-COMPs include bla KPC-2 , qnrS1 , tet (A), qnrD1 , and floR . Notably, the bla KPC-2 carbapenemase gene was found in MITE-COMPs bounded by MITE244 and another MITE-COMP bounded by IS 101 . These findings highlight a potential role for MITEs in the spread of diverse ARGs in Enterobacteriaceae .