The Insertion Sequence Excision Enhancer (IEE): a PrimPol-based system for Immobilizing Transposon-Transmitted Antibiotic Resistance Genes?

We provide an overview of a protein, IEE (Insertion Sequence Excision Enhancer), which was originally observed to facilitate high levels of excision of the IS3 family member, IS629, from clinically important Escherichia coli O157:H7. IEE was subsequently shown to affect a large class of bacterial insertion sequences which all transpose by producing a circular intermediate and presumably use the copy-out-paste-in transposition mechanism. Excision is dependent on both IEE and transposase indicating that it is associated with the transposition process itself. We propose that IEE serves to immobilize genes carried by compound transposons by removing the flanking IS copies, an activity which would explain the presence of certain of these genes without associated IS copies in plasmids and chromosomes. The biochemical activities of IEE as a primase with the capacity to recognize microhomologies, together with the observation that its effect appears to be restricted to those IS families which probably use the copy-out-paste-in transposition pathway, suggests a strand switch mechanism during the copy-out step leading to abortive transposition. This reinforces the proposal made for understanding the loss of the IS30 family member, ISApl1, which flanks the mcr-1 gene in the compound transposon Tn6330.