The biology of IncI2 plasmids shown by whole-plasmid multi-locus sequence typing

Authors: Meinersmann, Richard - Rick

Submitted to: Plasmid Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/24/2019
Publication Date: N/A
Citation: N/A

Interpretive Summary: In 2015 a newly discovered mechanism of bacterial resistance to colistin was described. This resistance was conferred by the gene mcr-1, which was found on plasmids. Finding the gene on a plasmid is important because these are independent extra-chromosomal pieces of DNA that replicate independently and may be readily transferred to other strains of bacteria. Transferable resistance to colistin is important because that is an antimicrobial that has been held in reserve to treat infections due to multi-resistant organisms and this raises the potential for resistance to colistin also becoming widespread. One kind of plasmid that has been found with mcr-1 is known as IncI2 plasmid. Tracing the lineage development of mcr-1 has not been possible based on the gene alone because all the mcr-1 genes that have been found are too homogeneous. However, a careful analysis of the whole plasmid was very revealing. A process known as a whole-plasmid multi-locus sequence type (wpMLST) system was developed for IncI2 plasmids. The analyses showed that transfer of IncI2 plasmids has been very frequent and that the transfer process may be opening up the plasmid to gain added genes such as mcr-1. Genes that are needed for cell-to-cell transfer were well maintained as were genes that contribute to biofilm formation. Genes that are considered accessory, not necessary for needed functions including mcr-1, showed evidence of multiple additions and losses by the plasmid. This recognition can help hinder the spread of the plasmid by knowing how to control factors that may give it a selective advantage.

Technical Abstract: IncI2 type plasmids are medium-sized (~55 - 80 kb) conjugative plasmids that have been found carrying important antimicrobial resistance genes but have also been frequently found as cryptic plasmids. The DNA sequences for 147 fully sequenced IncI2 plasmids were studied by a whole-plasmid multi-locus sequence typing (wpMLST) scheme. A total of 165 loci were identified of which 52 were considered core (carried by greater than 95% of the plasmids). Most of the plasmids carrying the antimicrobial gene mcr-1 were in a distinct clade while most of the antimicrobial gene free plasmids were fairly unrelated. However the parent strains of bacteria were disparate for both groups of plasmids, showing that conjugal transfer of IncI2 plasmid is frequent. The mcr-1 gene was likely to have been introduced into IncI2 plasmids multiple times. It was also observed that the genes for conjugation showed significant linkage disequilibrium despite substantial diversity for most of those genes. Genes associated with biofilm formation were also among the core genes. Given the role conjugation can play in biofilm formation, it was concluded that conjugation is an active survival strategy for IncI2 plasmids. The IncI2 plasmid will have selective advantage when the plasmid-bearing bacteria are introduced to a new animal host that carries potential conjugal mates.