A Novel Family of Acinetobacter Mega-Plasmids Are Disseminating Multi-Drug Resistance Across the Globe While Acquiring Location-Specific Accessory Genes.

Acinetobacter species are emerging as major nosocomial pathogens, aided by their ability to acquire resistance to all classes of antibiotics. A key factor leading to their multi-drug resistance phenotypes is the acquisition of a wide variety of mobile genetic elements, particularly large conjugative plasmids. Here, we characterize a family of 21 multi-drug resistance mega-plasmids in 11 different Acinetobacter species isolated from various locations across the globe. The plasmid family exhibits a highly dynamic and diverse accessory genome, including 221 antibiotic resistance genes (ARGs) that confer resistance to 13 classes of antibiotics. We show that plasmids isolated within the same geographic region are often evolutionarily divergent members of this family based on their core-genome, yet they exhibit a more similar accessory genome. Individual plasmids, therefore, can disseminate to different locations around the globe, where they then appear to acquire diverse sets of accessory genes from their local surroundings. Further, we show that plasmids from several geographic regions were enriched with location-specific functional traits. Together, our findings show that these mega-plasmids can transmit across species boundaries, have the capacity for global dissemination, can accumulate a diverse suite of location-specific accessory genes, and can confer multi-drug resistance phenotypes of significant concern for human health. We therefore highlight this previously undescribed plasmid family as a serious threat to healthcare systems worldwide. These findings also add to the growing concern that mega-plasmids are key disseminators of antibiotic resistance and require global surveillance.

Preclinical class 1 integron with a complete Tn402-like transposition module.

The presence of integrons was assessed in gut bacteria isolated from wild-caught prawns. A pseudomonad was recovered that contained a Tn402-like class 1 integron with a complete transposition module and two gene cassettes. One cassette was identical to a previously described cassette from a chromosomal class 3 integron in Delftia tsuruhatensis.

Mobilization of a Tn402-like class 1 integron with a novel cassette array via flanking miniature inverted-repeat transposable element-like structures.

A Tn402-like class 1 integron was recovered from a prawn-associated bacterium. One of its cassettes included methionine sulfoxide reductase genes, the first example of such genes being captured by an integron. The integron was flanked by direct repeats that resemble miniature inverted-repeat transposable element sequences. Excision of the integron by homologous recombination through these sequences was demonstrated.