Derepressed transfer properties leading to the efficient spread of the plasmid encoding carbapenemase OXA-48

Abstract

The current emergence of the carbapenemase OXA-48 among Enterobacteriaceae is related to the spread of a single IncL/M-type plasmid, pOXA-48a. This plasmid harbors the blaOXA-48 gene within a composite transposon, Tn1999, which is inserted into the tir gene, encoding a transfer inhibition protein. We showed that the insertion of Tn1999 into the tir gene was involved in a higher transfer frequency of plasmid pOXA-48a. This may likely be the key factor for the successful dissemination of this plasmid.

FIG 1

Design of primers for amplification of the tir gene. The −35 and −10 sequences of the promoter of the tir gene are indicated in boldface type and are shaded in gray. Nucleotides modified or added in primer preTIR-For are underlined. The orientation of the primers is indicated by arrows.

FIG 2

Promoter structures for the tir gene in plasmids pOXA-48a (a) and pNDM-OM (b). The −35 and −10 sequences of the promoter are indicated in boldface type and are shaded in gray. The +1 transcription start sites are indicated in boldface type.

FIG 3

Mean relative expression ratio of the traM (b) and the tir genes (c) for E. coli TOP10(pOXA-48a) compared to E. coli TOP10(pNDM-OM). The expression level of the gap gene (a) in E. coli TOP10 was used as a reference with a value of 1.