IS CR Elements: Novel Gene-Capturing Systems of the 21st Century?

Abstract

SUMMARY “Common regions” (CRs), such as Orf513, are being increasingly linked to mega-antibiotic-resistant regions. While their overall nucleotide sequences show little identity to other mobile elements, amino acid alignments indicate that they possess the key motifs of IS 91 -like elements, which have been linked to the mobility ent plasmids in pathogenic Escherichia coli . Further inspection reveals that they possess an IS 91 -like origin of replication and termination sites ( ter IS), and therefore CRs probably transpose via a rolling-circle replication mechanism. Accordingly, in this review we have renamed CRs as IS CR s to give a more accurate reflection of their functional properties. The genetic context surrounding IS CR s indicates that they can procure 5′ sequences via misreading of the cognate ter IS, i.e., “unchecked transposition.” Clinically, the most worrying aspect of IS CR s is that they are increasingly being linked with more potent examples of resistance, i.e., metallo-β-lactamases in Pseudomonas aeruginosa and co-trimoxazole resistance in Stenotrophomonas maltophilia . Furthermore, if IS CR elements do move via “unchecked RC transposition,” as has been speculated for IS CR 1, then this mechanism provides antibiotic resistance genes with a highly mobile genetic vehicle that could greatly exceed the effects of previously reported mobile genetic mechanisms. It has been hypothesized that bacteria will surprise us by extending their “genetic construction kit” to procure and evince additional DNA and, therefore, antibiotic resistance genes. It appears that IS CR elements have now firmly established themselves within that regimen.