TnAbaR1: a novel Tn7-related transposon in Acinetobacter baumannii that contributes to the accumulation and dissemination of large repertoires of resistance genes
Department of Infection, Immunity and Inflammation, University of Leicester, UK
29 Sept 2009
19 Jan 2010
23 Feb 2010
Acinetobacter baumannii, antibiotic resistance, transposon, Tn7
Acinetobacter baumannii is an opportunistic bacterial pathogen that is a frequent cause of severe hospital-associated infections. Treatment is problematic given the organism's cunning ability to acquire antibiotic resistance. Indeed, strains resistant to almost all antibiotics have already emerged. Several A. baumannii strains for which the genome sequence has been determined contain large clusters of chromosomally integrated resistance genes. AbaR1, the archetypal A. baumannii ‘resistance island’ found in strain AYE, harbours 45 resistance genes. We investigated the hypothesis that AbaR1-like islands were mobile. Many chromosomally integrated elements exhibit low frequency spontaneous excision. However, use of a highly sensitive PCR assay targeting the hypothesized empty integration site failed to reveal evidence of excision in any of the island-bearing strains examined, suggesting that if excision was occurring it was extremely rare. Bioinformatics analyses of island termini across multiple strains suggested that these islands had arisen from an ancestral transposon, distantly related to Tn7, which had accumulated, often in a nested fashion, multiple transposons, integrons and resistance gene cassettes. Accordingly, we have renamed AbaR1 as TnAbaR1. The first three of the five tandem genes located at the 3′-comM terminus of TnAbaR1 showed marked similarities at a Blastp and/or domain level to their cognate transposition-associated partners in Tn7. TnAbaR1 also shared other Tn7 features: short imperfect terminal inverted repeats, site-specific insertion, flanking 5 bp (base pair) perfect direct repeats and rare-to-non-existent spontaneous excision. Tn7-related transposons are highly promiscuous given their ability to exploit two distinct mobilization pathways—stable integration into a unique chromosomal site or homing onto conjugative plasmids for onward transfer to a new host. With a single known exception, TnAbaR1-like transposons map uniquely to the comM gene. However, we have now identified a multidrug-resistant A. baumannii strain harbouring two TnAbaR1-like transposons, both located at completely novel loci, further substantiating the mobile TnAbaR1 hypothesis. TnAbaR1-like elements have undoubtedly contributed to the rapid emergence of antibiotic resistance in this increasing important human pathogen. Ominously, like its distant relative Tn7, TnAbaR1 may exhibit the potential to jump bacterial species readily, thus posing the risk of widespread dissemination of large, single assemblage repositories of resistance genes and threatening the emergence of a post-antibiotic era.