ISAba825 controls the expression of the chromosomal b/aOXA-51-like and the plasmid borne blaOXA-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 b/aOXA-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 b/aOXA-58-like and the b/aOXA-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-b/aOXA-58-like genes but during that same process also lost the chromosomal ISAba825 element present upstream of the b/aOXA-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 b/aOXA-65 gene and the b/aOXA-58-like gene expression and also highlights the importance of this element in carbapenem-sensitive isogenic strains, which were once carbapenem resistant.