Evolution of a novel plasmid-borne genetic platform carrying blaNDM-1 in a carbapenem-resistance Acinetobacter bereziniae clinical strain isolated in Rosario

BROVEDAN, M; MARCHIARO P; MORAN-BARRIO, J.; BRAMBILLA, L; CERA, G.; RINAUDO, M; VIALE, A; LIMANSKY, A

Congreso; XI Congreso Argentino de Microbiología General; 2015

The emergence of Gram-negative clinical species harboring blaNDM-1 gene encoding the metallo-β-lactamase NDM-1 has aroused public concern worldwide. Complete sequencing of plasmids carrying blaNDM-1 provides important information of its genetic environment and a better understanding of its spread. We characterize here a novel plasmid, pNDM229, containing blaNDM-1 isolated from a carbapenem resistant-Acinetobacter bereziniae clinical strain (HPC229) in Rosario, Argentina from an immunocompromised female inpatient. We also compare here the blaNDM-1-containing genetic platform of pNDM229 with those present in other Acinetobacter plasmids. The whole genome sequencing of HPC229 disclosed the presence of blaNDM-1 in a 44,560 bp plasmid containing 53 predicted ORFs, from which 31 encode proteins with BLAST scores compatible to sequences of attributed functions in databases. Phylogenetic analysis using representative N-terminal relaxase domains from the different MOB families indicated a close affiliation of the pNDM229 relaxase (TraA) to the MOBQ1 family, characteristic of broad host range plasmids. The immediate genetic environment of pNDM229 blaNDM-1 was similar to those reported previously for pNDM-BJ01-like plasmids (1). However, some differences were noted between all these plasmids including variations downstream of the Tn125 element such as: i) a novel copy of ISAba14-like in pNDM229, ii) an extra ISAba125 copy in A. baumannii pAbNDM, and iii) the absence of 3´ ISAba125 in pM131_NDM1 and its replacement by a ISAba11. Other relevant differences between the above plasmids include deletions involving a number of genes composing the blaNDM-1-containing platforms. Still, two regions are identical in all analyzed platforms which comprise from the ISAba14 element located upstream of the Tn125 to blaNDM-1, and the last 134-bp of its 3?end suggesting a common origin for these arrangements. Interestingly, the fact that the blaNDM-1-containing Tn125 in pNDM229 is bracketed by two ISAba14-like suggests that this structure forms a novel composite transposon which could move itself as a whole. The presence of an ISAba14-like copy in the HPC229 chromosome suggests that this novel arrangement could have been formed recently in this A. bereziniae strain. Finally, we propose that the mobilization of plasmids harboring blaNDM-1 among different Acinetobacter hosts could account for the genetic variations (indels) observed in the above described blaNDM-1-containing platforms. 1-Jones et al., Antimicrob Agents Chemother. 2015. 59:923-929.