Dataset Information

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

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.

SUBMITTER: Ghaly TM

PROVIDER: S-EPMC7738440 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Ghaly Timothy M TM Paulsen Ian T IT Sajjad Ammara A Tetu Sasha G SG Gillings Michael R MR

Frontiers in microbiology 20201202

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 fa ...[more]

PMID: 33343549

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Project description:Acinetobacter baumannii is an emergent bacterial pathogen that provokes many types of infections in hospitals around the world. The genome of this organism consists of a chromosome and plasmids. These plasmids vary over a wide size range and many of them have been linked to the acquisition of antibiotic-resistance genes. Our bioinformatic analyses indicate that A. baumannii plasmids belong to a small number of plasmid lineages. The general structure of these lineages seems to be very stable and consists not only of genes involved in plasmid maintenance functions but of gene sets encoding poorly characterized proteins, not obviously linked to survival in the hospital setting, and opening the possibility that they improve the parasitic properties of plasmids. An analysis of genes involved in replication, suggests that members of the same plasmid lineage are part of the same plasmid incompatibility group. The same analysis showed the necessity of classifying the Rep proteins in ten new groups, under the scheme proposed by Bertini et al. (2010). Also, we show that some plasmid lineages have the potential capacity to replicate in many bacterial genera including those embracing human pathogen species, while others seem to replicate only within the limits of the Acinetobacter genus. Moreover, some plasmid lineages are widely distributed along the A. baumannii phylogenetic tree. Despite this, a number of them lack genes involved in conjugation or mobilization functions. Interestingly, only 34.6% of the plasmids analyzed here possess antibiotic resistance genes and most of them belong to fourteen plasmid lineages of the twenty one described here. Gene flux between plasmid lineages appears primarily limited to transposable elements, which sometimes carry antibiotic resistance genes. In most plasmid lineages transposable elements and antibiotic resistance genes are secondary acquisitions. Finally, broad host-range plasmids appear to have played a crucial role.

Project description:Acinetobacter baumannii has become one of the most important multidrug-resistant nosocomial pathogens all over the world. Nonetheless, very little is known about the diversity of A. baumannii lineages coexisting in hospital settings. Here, using whole-genome sequencing, epidemiological data, and antimicrobial susceptibility tests, we uncover the transmission dynamics of extensive and multidrug-resistant A. baumannii in a tertiary hospital over a decade. Our core genome phylogeny of almost 300 genomes suggests that there were several introductions of lineages from international clone 2 into the hospital. The molecular dating analysis shows that these introductions happened in 2006, 2007, and 2013. Furthermore, using the accessory genome, we show that these lineages were extensively disseminated across many wards in the hospital. Our results demonstrate that accessory genome variation can be a very powerful tool for conducting genomic epidemiology. We anticipate future studies employing the accessory genome along with the core genome as a powerful phylogenomic strategy to track bacterial transmissions over very short microevolutionary scales. IMPORTANCE Whole-genome sequencing for epidemiological investigations (genomic epidemiology) has been of paramount importance to understand the transmission dynamics of many bacterial (and nonbacterial) pathogens. Commonly, variation in the core genome, single nucleotide polymorphisms (SNPs), is employed to carry out genomic epidemiology. However, at very short periods of time, the core genome might not have accumulated enough variation (sufficient SNPs) to tell apart isolates. In this scenario, gene content variation in the accessory genome can be an option to conduct genomic epidemiology. Here, we used the accessory genome, as well as the core genome, to uncover the transmission dynamics of extensive and multidrug-resistant A. baumannii in a tertiary hospital for a decade. Our study shows that accessory genome variation can be a very powerful tool for conducting genomic epidemiology.

Dataset Information

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

Publications

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

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