Abstract
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.
Highlights
Acinetobacter is a diverse genus of bacteria that commonly occur in soil and water, and in association with animals and plants (Fondi et al, 2010)
We collected an additional 17 publicly available complete plasmid sequences within this family, isolated from various locations across the world. This previously undescribed mega-plasmid family, found in 11 different Acinetobacter species so far, shares a tight core-genome, yet varies extensively in its accessory genome. We show that this plasmid family can rapidly disperse around the globe, where it subsequently accumulates a diverse suite of niche-adaptive accessory genes
We have identified four of the 21 plasmids to be part of the Rep-3 superfamily group, based on their replication initiation (Rep) protein
Summary
Acinetobacter is a diverse genus of bacteria that commonly occur in soil and water, and in association with animals and plants (Fondi et al, 2010). One of the key features leading to their multi-drug resistance is the acquisition of a wide variety of mobile DNA elements (Fournier et al, 2006; Hamidian et al, 2014, 2016; Lean and Yeo, 2017). Acinetobacter strains are known to harbor a strikingly diverse pool of plasmids (Fournier et al, 2006; Fondi et al, 2010; Merino et al, 2010; Lean and Yeo, 2017; Salto et al, 2018)
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