ISAba1 and Tn6168 acquisition by natural transformation leads to third-generation cephalosporins resistance in Acinetobacter baumannii

Acinetobacter baumannii has intrinsic beta-lactamase genes, namely ampC and bla_OXA-51-like, which are only strongly expressed when the ISAba1 insertion sequence is upstream the 5' end of the genes. A second ampC gene has also been identified in some clinical A. baumannii strains. The increased expression of these genes leads to resistance to beta-lactams, including third-generation cephalosporins and/or carbapenems. The aim of this work was to assess the involvement of natural transformation in the transfer of chromosomal ampC-associated mobile elements, and related changes in the resistance profile of recipient cells. Natural transformation assays with the naturally competent A. baumannii A118 clinical isolate as recipient cell and the multidrug resistant A. baumannii Ab51 clinical isolate as the source of donor DNA produced transformants. All tested transformants showed integration of the ISAba1 close to the ampC gene. In two transformants, the ISAba1 was acquired by transposition and inserted between the usual folE and the ampC genes. The remaining transformants acquired the ISAba1 adjacent to a second ampC gene, as part of Tn6168, likely by homologous recombination. Our study demonstrates that natural transformation can contribute to the widespread of beta-lactams resistance, and acquisition of non-resistant determinants can lead to changes in the susceptibility profile of A. baumannii strains.