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Title: Proposed model for the high rate of rearrangement and rapid migration observed in some IncA/C plasmid lineages

item Meinersmann, Richard - Rick
item LINDSEY, REBECCA - Former ARS Employee
item Bono, James - Jim
item Smith, Timothy - Tim
item Oakley, Brian

Submitted to: Applied and Environmental Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/27/2013
Publication Date: 8/30/2013
Citation: Meinersmann, R.J., Lindsey, R., Bono, J.L., Smith, T.P., Oakley, B. 2013. Proposed model for the high rate of rearrangement and rapid migration observed in some IncA/C plasmid lineages. Applied and Environmental Microbiology. 79(16):4806-4814.

Interpretive Summary: Plasmids are pieces of DNA that are independent of the main chromosome in bacteria. Plasmids are important because they are often exchanged between different families of bacteria and because they usually carry genes that give the bacteria a survival or growth advantage, such as antimicrobial resistance genes. Plasmids also appear to be able to rapidly change the genes they carry, gaining or losing genes including the antimicrobial resistance genes. How these changes occur and what regulates the changes is not known but it will help control the spread of injurious genes if we better understand this phenomenon. Plasmids occur in about two-dozen different classes called incompatibility groups (Inc groups). IncA/C plasmids are a group that is common in bacteria that infect the gastrointestinal tract, are larger than most plasmids, and usually carry multiple antimicrobial resistance genes. To develop a model of how these plasmids evolved we determined the DNA sequence for 39 recently isolated IncA/C plasmids and compared these with each other and 26 more sequences that are publicly available. We were able to distinguish six different lineages. The largest lineage appeared to be the most recent lineage to have evolved and is spreading extremely rapidly. The pattern of changes made it clear that the major situation that leads to change is during the transfer of the plasmid from one strain to another strain of bacteria. This study showed how IncA/C plasmids are related to each other so that tracking the plasmids should be easier. Also, the ultimate goal of controlling the plasmids will benefit most from interrupting bacterial transfer between different strains of bacteria. This information contributes to physicians, veterinarians and industrial and academic scientists understanding how changes in antimicrobial resistance occurred over time.

Technical Abstract: IncA/C plasmids are a class of plasmids from Enterobacteraciae that are relatively large (49 to >180 kbp), are readily transferred by conjugation, and carry multiple antimicrobial resistance genes. Reconstruction of the phylogeny of these plasmids has been difficult because of the high rate of remodeling by recombination-mediated horizontal gene transfer (HGT). We hypothesized that evaluation of nucleotide polymorphisms relative to the rate of HGT would help to develop a clock to show if modern practices have had significant influences on the lineages of the plasmid. A system was developed to rapidly sequence up to 191 known open-reading-frames from each of 39 recently isolated IncA/C plasmids from a diverse panel of Salmonella enterica and Escherichia coli. With these data plus sequences from Genbank we were able to distinguish six distinct lineages that had extremely low numbers of polymorphisms within each lineage, especially among the largest group that we designated as Lineage 1. Two regions, each about half the plasmid in size, could be distinguished with a separate lineal pattern. The distribution of Lineage 1 showed that it has migrated extremely rapidly with fewer polymorphisms than can be expected in a thousand years. Remodeling by frequent HGT was clearly evident with a pattern that appeared to have the highest rate just upstream of the putative conjugation origin of transfer (ori-T). Thus it seems likely that when an IncA/C plasmid is transferred by conjugation there is an opportunity for plasmid re-modeling adjacent to the ori-T, which is also adjacent to a multiple antimicrobial resistance gene cassette.