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Emergence of Tn1999.7, a New Transposon in blaOXA-48-Harboring Plasmids Associated with Increased Plasmid Stability

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OXA-48 is the most common carbapenemase in Enterobacterales in Germany and many other European countries. Depending on the genomic location of blaOXA-48, OXA-48-producing isolates vary in phenotype and intra- and… Click to show full abstract

OXA-48 is the most common carbapenemase in Enterobacterales in Germany and many other European countries. Depending on the genomic location of blaOXA-48, OXA-48-producing isolates vary in phenotype and intra- and interspecies transferability of blaOXA-48. In most bacterial isolates, blaOXA-48 is located on one of seven variants of Tn1999 (Tn1999.1 to Tn1999.6 and invTn1999.2). ABSTRACT OXA-48 is the most common carbapenemase in Enterobacterales in Germany and many other European countries. Depending on the genomic location of blaOXA-48, OXA-48-producing isolates vary in phenotype and intra- and interspecies transferability of blaOXA-48. In most bacterial isolates, blaOXA-48 is located on one of seven variants of Tn1999 (Tn1999.1 to Tn1999.6 and invTn1999.2). Here, a novel Tn1999 variant, Tn1999.7, is described, which was identified in 11 clinical isolates from 2016 to 2020. Tn1999.7 differs from Tn1999.1 by the insertion of the 8,349-bp Tn3 family transposon Tn7442 between the lysR gene and blaOXA-48 open reading frame. Tn7442 carries genes coding for a restriction endonuclease and a DNA methyltransferase as cargo, forming a type III restriction modification system. Tn1999.7 was carried on an ~71-kb IncL plasmid in 9/11 isolates. In one isolate, Tn1999.7 was situated on an ~76-kb plasmid, harboring an additional insertion sequence in the plasmid backbone. In one isolate, the plasmid size is only ~63 kb due to a deletion adjacent to Tn7442 that extends into the plasmid backbone. Mean conjugation rates of the Tn1999.7-harboring plasmids in J53 ranged from 4.47 × 10−5 to 2.03 × 10−2, similar to conjugation rates of other pOXA-48-type IncL plasmids. The stability of plasmids with Tn1999.7 was significantly higher than that of a Tn1999.2-harboring plasmid in vitro. This increase in stability could be related to the insertion of a restriction-modification system, which can promote postsegregational killing. The increased plasmid stability associated with Tn1999.7 could contribute to the further spread of OXA-48.

Keywords: blaoxa; tn1999 tn1999; increased plasmid; stability; harboring plasmids; tn1999

Journal Title: Antimicrobial Agents and Chemotherapy
Year Published: 2022

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