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 anthropic practices have had significant influences on the lineages of the plasmid. A system was developed to rapidly sequence up to 191 known open27 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 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 two-thousand years. Remodeling by frequent HGT was evident with a pattern that appeared to have the highest rate just upstream of the putative conjugation origin of transfer (ori-T). It seems likely that when an IncA/C plasmid is transferred also adjacent to a multiple antimicrobial resistance gene cassette.
