A final example of the subtle line dividing IS and transposons is found in the IS91/ISCR group (Fig 1.17.1). IS91 was identified some time ago (Diaz-Aroca, et al., 1984) and carries a single Tpase orf. More recently, a group of related elements, ISCR (IS with a "Common Region") was described [reviewed in (Toleman, et al., 2006, Toleman & Walsh, 2010)]. Although there has been no formal demonstration that these actually transpose, the CR is an orf which resembles the IS91 family Tpases (Chandler, et al., 2013). The major feature of ISCR elements is that they are associated with a diverse variety of antibiotic resistance genes and, particularly in the case of Pseudomonas ISCR, aromatic degradation pathways, both upstream and downstream of the Tpase orf.

It is thought that these genes are transmitted during the rolling circle type of transposition mechanism postulated to occur in IS91 transposition (Fig 1.17.2). This involves an initiation event at one IS end, polarized transfer of the IS strand into a target molecule and termination at the second end (Garcillan-Barcia, et al., 2002). However, the de la Cruz lab has identified circular IS91 forms and it seems possible that these are transposition intermediates. An alternative model involving transposon circle formation is shown in Fig 1.17.3. This model is attractive since it would liberate the transposon circle intermediate to locating a target site following circle formation rather than requiring target engagement during the replicative transposition process (Fig. 1.17.2)

Flanking gene acquisition is thought to occur when the termination mechanism fails and rolling circle transposition extends into neighboring DNA where it may encounter a second surrogate end (Garcillan-Barcia, et al., 2002). This type of mobile element may prove to play an important role in the assembly and transmission of multiple antibiotic resistance (Toleman, et al., 2006, Toleman & Walsh, 2011).

References :

• Chandler M, de la Cruz F, Dyda F, Hickman AB, Moncalian G & Ton-Hoang B (2013) Breaking and joining single-stranded DNA: the HUH endonuclease superfamily. Nat Rev Microbiol 11: 525-538.
• Diaz-Aroca E, de la Cruz F, Zabala JC & Ortiz JM (1984) Characterization of the new insertion sequence IS91 from an alpha- hemolysin plasmid of Escherichia coli. Mol.Gen.Genet. 193: 493-499.
• Garcillan-Barcia MP, Bernales I, Mendiola MV & De la Cruz F (2002) IS91 rolling circle transposition. Mobile DNA, Vol. II (Craig NL, Craigie R, Gellert M & Lambowitz A, eds.), pp. 891-904. ASM press, Washington DC.
• Toleman MA & Walsh TR (2010) ISCR elements are key players in IncA/C plasmid evolution. Antimicrob Agents Chemother 54: 3534; author reply 3534.
• Toleman MA & Walsh TR (2011) Combinatorial events of insertion sequences and ICE in Gram-negative bacteria. FEMS Microbiol Rev 35: 912-935.
• Toleman MA, Bennett PM & Walsh TR (2006) ISCR Elements: Novel Gene-Capturing Systems of the 21st Century? Microbiol Mol Biol Rev 70: 296-316.