Transposition of Tn 125 Encoding the NDM-1 Carbapenemase in Acinetobacter baumannii

Abstract

The bla NDM-1 gene encodes a carbapenemase that confers resistance to almost all ␤-lactams, including last-resort carbapenems. This is increasingly reported worldwide in nosocomial and community-acquired Gram-negative bacteria. Acinetobacter baumannii is an important opportunistic pathogen that is considered an intermediate reservoir for the bla NDM-1 gene. In this species, the bla NDM-1 gene is located within the Tn125 composite transposon. The mechanism driving the mobility of Tn125 has not yet been elucidated. Here we experimentally demonstrated the transposition of Tn125 in A. baumannii. Systematic 3-bp duplication of the target site, being the signature of transposition, was evidenced. The target site consensus sequence for Tn125 transposition was found to be GC enriched at the duplicated 3 bp and AT rich in the vicinity. Transposition frequency was not influenced by temperature changes or by exposure to subinhibitory concentrations of various antibiotics. This work is the first direct evidence of the functionality of a composite transposon in A. baumannii. It provides a mechanistic clue for the dissemination of the bla NDM-1 gene in Acinetobacter spp. and subsequently among Enterobacteriaceae.

IS26-Mediated Transfer of blaNDM–1 as the Main Route of Resistance Transmission During a Polyclonal, Multispecies Outbreak in a German Hospital

“…It is assumed that the high prevalence of ISAba125 in Acinetobacter spp. genomes indicates frequent transposition events, the presence of HGT, a replicative transposition mechanism, and the ability of ISAba125 to expand within genomes (Bontron et al, 2016). In the present study we found this genuine Tn125 structure slightly changed by the integration of IS26 into each ISAba125 element (Figure 4).…”

“…These regions were located upstream the antibiotic resistance island ARI-A that mainly affected genes coding for conjugative transfer proteins (Supplementary Image 1). Within ARI-A, we found the bla NDM-1 gene located on a previously described Tn125 transposon structure (Bontron et al, 2016). This structure, however, was consistently flanked by two IS26 elements which were integrated into the adjacent ISAba125 elements of Tn125 (Figure 4).…”

“…A more detailed analysis of the plasmids of the present study showed that bla NDM-1 is located in a conserved sequence within the ARI-A of IncA/C2 and various sites of IncN plasmids, respectively (Figure 4 and Supplementary Image 1). This structure has been previously described as Tn125 (Bontron et al, 2016). In 2016, Bontron et al (2016) demonstrated that the Tn125 composite transposon can efficiently transpose within A. baumanii which most likely serves as an intermediate reservoir for the bla NDM-1 gene.…”

“…In 2016, Bontron et al (2016) demonstrated that the Tn125 composite transposon can efficiently transpose within A. baumanii which most likely serves as an intermediate reservoir for the bla NDM-1 gene. The genetic organization of Tn125 is defined by terminal ISAba125 elements that have been shown to be functional for transposition (Bontron et al, 2016). It is assumed that the high prevalence of ISAba125 in Acinetobacter spp.…”

Antibiotic Resistance and Mobile Genetic Elements in Extensively Drug-Resistant Klebsiella pneumoniae Sequence Type 147 Recovered from Germany

“…Moreover, b la NDM-1 in K. pneumoniae has been mainly associated with broad host range IncA/C2, IncHI1, IncX3 and IncN2 plasmids [ 4 ]. In Acinetobacter baumannii, the transposon Tn 125, harbouring the insertion element IS Aba125, is considered as the main vehicle for the dissemination of NDM-1 enzymes [ 5 , 6 ].…”