Variants of Tn6924, a Novel Tn7 Family Transposon Carrying the bla(NDM) Metallo-beta-Lactamase and 14 Copies of the aphA6 Amikacin Resistance Genes Found in Acinetobacter baumannii

Microbiology spectrum(2022)

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摘要
Carbapenem resistance in Acinetobacter baumannii is primarily due to the global spread of two main clones that carry oxa23, oxa24, and oxa58. However, new carbapenem-resistant clones are emerging that are also resistant to a wide range of antibiotics. Strains belonging to ST85(IP) (Institut Pasteur) carry the bla(NDM) metallo-beta-lactamase carbapenem resistance gene. Here, we completed the genome sequence of an ST85(IP) strain, CI300, recovered in 2015 in Lebanon, using a combination of Illumina MiSeq and Oxford Nanopore sequencing and a hybrid assembly approach. CI300 is highly resistant to meropenem and amikacin, and consistent with this, a copy of the bla(NDM) carbapenem and 14 copies of the aphA6 amikacin resistance genes were found in the genome. CI300 also contains the sul2 sulfonamide and the msr(E) macrolide resistance genes. All aphA6 copies and bla(NDM) are in a novel 76-kb Tn7 family transposon designated Tn6924. Like Tn7, Tn6924 is bounded by 29-bp inverted repeats with additional TnsB binding sites at each end. Several variants of Tn6924 were found in a set of diverse strains, including ST85(IP) strains as well as members of global clones 1 and 2. sul2 and msr(E) are in a 13.0-kb pseudocompound transposon (PCT) bounded by IS1008. ST85s represent a diverse group of strains, particularly in their antibiotic resistance gene content and the K and OC surface polysaccharide loci. Acquisition of Tn6924 by members of global clones indicates the significance of this transposon in spreading two clinically significant resistance genes, bla(NDM )and aphA6. IMPORTANCE To date, efforts to study the resistance mechanisms of carbapenem-resistant Acinetobacter baumannii have been largely focused on the two major globally distributed clones (GC1 and GC2). ST85 is an emerging sequence type, and unlike other clones, it is associated with the carriage of the bla(NDM) gene. Here, we completed the genome sequence of an ST85 strain and showed that bla(NDM) and 14 copies of the aphA6 amikacin resistance genes are in Tn6924, a novel Tn7 family transposon. Analysis of all publicly available ST85s predicted that all strains in the main lineage carry a variant of Tn6924. Variants of Tn6924 were also found in other clones, including GC1 and GC2. Tn6924 is an important mobile element given that it carries two clinically important resistance genes (bla(NDM) and aphA6) and has spread to other clones. Therefore, outbreaks caused by ST85s should be studied and tracked.
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关键词
Acinetobacter baumannii, aminoglycoside resistance, carbapenem resistance, aphA6, bla(NDM), antibiotic resistance, Tn6924
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