ISAba825 controls the expression of the chromosomal bla_OXA-51-like and the plasmid borne bla_OXA-58 gene in clinical isolates of Acinetobacter baumannii isolated from the USA

Four non-repetitive, clonally related (ST114), carbapenem-resistant Acinetobacter baumannii strains isolated in the USA were examined to understand the mechanisms of carbapenem resistance including screening for the presence of an insertion sequence upstream of the bla_OXA-51-like gene, which could be involved in the control and expression of the antibiotic-resistance gene. We observed that the main mechanisms of carbapenem resistance were the result of the over-expression of the bla_OXA-58-like and the bla_OXA-65 gene, both of which had the presence of ISAba825 upstream of the genes. The importance of this element was shown by isolating plasmid-cured isogenic strains that had lost the plasmid with the ISAba825-bla_OXA-58-like genes but during that same process also lost the chromosomal ISAba825 element present upstream of the bla_OXA-65 gene. A 16-fold decrease in minimum inhibitory concentration of imipenem and an eight-fold decrease in the minimum inhibitory concentration of meropenem were seen in the isogenic strains that lost the plasmid. The study presents the first report of ISAba825 simultaneously governing the bla_OXA-65 gene and the bla_OXA-58-like gene expression and also highlights the importance of this element in carbapenem-sensitive isogenic strains, which were once carbapenem resistant.