IS 26 and the IS 26 family: versatile resistance gene movers and genome reorganizers

Abstract

SUMMARY In Gram-negative bacteria, the insertion sequence IS 26 is highly active in disseminating antibiotic resistance genes. IS 26 can recruit a gene or group of genes into the mobile gene pool and support their continued dissemination to new locations by creating pseudo-compound transposons (PCTs) that can be further mobilized by the insertion sequence (IS). IS 26 can also enhance expression of adjacent potential resistance genes. IS 26 encodes a DDE transposase but has unique properties. It forms cointegrates between two separate DNA molecules using two mechanisms. The well-known copy-in (replicative) route generates an additional IS copy and duplicates the target site. The recently discovered and more efficient and targeted conservative mechanism requires an IS in both participating molecules and does not generate any new sequence. The unit of movement for PCTs, known as a translocatable unit or TU, includes only one IS 26 . TU formed by homologous recombination between the bounding IS 26 s can be reincorporated via either cointegration route. However, the targeted conservative reaction is key to generation of arrays of overlapping PCTs seen in resistant pathogens. Using the copy-in route, IS 26 can also act on a site in the same DNA molecule, either inverting adjacent DNA or generating an adjacent deletion plus a circular molecule carrying the DNA segment lost and an IS copy. If reincorporated, these circular molecules create a new PCT. IS 26 is the best characterized IS in the IS 26 family, which includes IS 257 /IS 431 , ISSau10, IS 1216 , IS 1006 , and IS 1008 that are also implicated in spreading resistance genes in Gram-positive and Gram-negative pathogens.

Distribution and expression of the aac(6′)-Im (aacA16) aminoglycoside resistance gene

“…However, in all the cases reported to date (Figure 1 ), it has been truncated by IS 26 , which is now often found surrounding parts of class 1 integrons and has even taken over their re-location. 20 How the region was introduced into A. baumannii remains to be established but it seems likely that it was brought in by a broad host range Enterobacterial plasmid. Although the plasmids found in Enterobacteria, such as IncHI2, IncC and IncM plasmids, have not been found stably maintained in A. baumannii , there are examples of fragments of such plasmids being found incorporated into the A. baumannii genome.…”

“… 21 , 22 Indeed, these regions have been excised by the action of IS 26 , and IS 26 appears to be the predominant mobile element that has introduced further resistance genes into A. baumannii . 20 …”