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 IS91-like elements, which have been linked to the mobility ent plasmids in pathogenic Escherichia coli. Further inspection reveals that they possess an IS91-like origin of replication and termination sites (terIS), and therefore CRs probably transpose via a rolling-circle replication mechanism. Accordingly, in this review we have renamed CRs as ISCRs to give a more accurate reflection of their functional properties. The genetic context surrounding ISCRs indicates that they can procure 5′ sequences via misreading of the cognate terIS, i.e., “unchecked transposition.” Clinically, the most worrying aspect of ISCRs 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 ISCR elements do move via “unchecked RC transposition,” as has been speculated for ISCR1, 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 ISCR elements have now firmly established themselves within that regimen.

Response of activated sludge to the treatment of oxytetracycline production waste stream

“…In this study, no tet genes were detected in any intI1 gene cassette arrays, which was consistent with previous studies (Toleman et al 2006). However, our previous work found that tet(A), tet(C), and tet(G) were positively correlated with intI1, which was assumed to be related with the insertion sequence common region (ISCR), a newly highlighted complex integron element which can integrate non-cassette resistance genes and combine with intI1 to form complex integrons (Toleman et al 2006;Liu et al 2012).…”

“…However, our previous work found that tet(A), tet(C), and tet(G) were positively correlated with intI1, which was assumed to be related with the insertion sequence common region (ISCR), a newly highlighted complex integron element which can integrate non-cassette resistance genes and combine with intI1 to form complex integrons (Toleman et al 2006;Liu et al 2012). In the present study, the abundance of intI1 and ISCR1 increased after OTC exposure, indicating that they may perform certain gene transfer functions under high OTC selection pressure, which requires more research.…”

Novel Class 1 Integrons in Multi-drug Resistant Isolates from Eastern China

“…This result implied that there may be other mechanisms responsible for bacterial resistance. Resistance to antibiotics could be due to chromosome mutation, lack of drug penetration, or resistance genes that were located in the chromosome or related to other mobile genetic elements such as insertion sequences, transposons and plasmids [18,19].…”

Novel 16S rRNA Methyltransferase RmtH Produced by Klebsiella pneumoniae Associated with War-Related Trauma

“…To our knowledge, this is the first instance where a 16S RMTase gene was found in association with ISCR2. ISCR2 is usually found intact upstream of a resistance gene, while the second copy downstream is typically truncated (14). Since ISCR2 possesses a KpnI restriction site, we were not able to assess whether the two copies of ISCR2 were intact or not.…”

“…ISCR2 is an IS91-like transposable element which is found in association with various resistance genes, including those for sulfonamide, trimethoprim, and florfenicol (14), and also tetracycline and cephalosporin (15,16). It is believed to facilitate mobilization of the genetic elements downstream.…”