|RICKER, NICOLE - University Of Guelph|
|CHALMERS, G - University Of Guelph|
|WHALER, ELLI - Retired ARS Employee|
|ALLEN, HEATHER - Retired ARS Employee|
|Meinersmann, Richard - Rick|
Submitted to: Antibiotics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/24/2022
Publication Date: 1/29/2022
Citation: Ricker, N., Chalmers, G., Whaler, E., Allen, H.K., Meinersmann, R.J. 2022. Genomic changes within a subset of IncI2 plasmids associated with dissemination of mcr-1 genes and other important AMR determinants. Antibiotics. https://doi.org/10.3390/antibiotics11020181.
Interpretive Summary: Bacteria often carry plasmids that are extra-chromosomal pieces of DNA that replicate independently of the chromosome. IncI2 plasmids are a type that have been associated with carrying genes for resistance to antimicrobials, such as extended spectrum beta-lactamases (ESBL) and colistin, that are considered "last resort" treatments. We have seen that certain lineages of the plasmid are more likely than others to carry the resistance genes. We characterized a population of the plasmids to see if the likelihood of carrying the resistance genes was simply a matter of inheritance or if there were characteristics of the plasmid that encouraged the placement of the resistance genes. Plasmids from Asia were more likely to carry resistance genes, probably due to more exposure to these antibiotics and because surveillance there is biased towards sequencing of resistant organisms. IncI2 plasmids from North America, which were sequenced without bias towards resistant organisms, were much less likely to carry resistance genes to ESBL and colistin. Those plasmids that did carry the resistance genes were more likely to also have insertion sequence (IS) elements with no direct association with the acquired resistance genes. Thus there appear to be properties of the plasmid structures that favor the accumulation of important antimicrobial resistance genes.
Technical Abstract: IncI2 plasmids appear to have only recently become associated with resistance genes; however, their tendency to carry resistance to the antibiotics of last resort and their widespread distribution increase their relative importance. In this study we describe lineages within this plasmid family that have an increased likelihood of acquisition of antimicrobial resistance genes. Globally distributed mcr-1-carrying IncI2 plasmids were found to cluster with other IncI2 plasmids carrying extended-spectrum beta-lactamase genes, and separately from the non-resistant IncI2 plasmids. In addition, IS elements with no direct association with the acquired resistance genes also clustered with the resistance plasmids in the phylogenetic tree. In recognition of the biased sequencing of resistant plasmids globally, the analysis was also performed on resistant and non-resistant IncI2 plasmids sequenced in the USA through government surveillance efforts that do not rely on antibiotic selection. This analysis confirmed a distinct clustering associated with both resistance and mobile elements, and identified possible genomic changes in core genes that correlate with increased acquisition of foreign DNA. This work highlights a potential genetic mechanism for increased uptake of foreign DNA within this prevalent family of plasmids.