General features and properties of insertion sequence elements

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IS and Gene Expression

Another important aspect of IS impact on their bacterial hosts is their ability to modulate gene expression. In addition to acting as vectors for gene transmission from one replicon to another in the form composite transposons (two IS flanking any gene; Fig 1.2.3) and tIS (Fig 1.13.1) and their ability to interrupt genes, it has been known for some time (Reif & Saedler, 1974, Glansdorff, et al., 1981) that IS can also activate gene expression. This capacity has recently received much attention due to the increase in resistance to various antibacterials (Aubert, et al., 2006, Soki, et al., 2013), a worrying public health threat (Kieny, 2012, McKenna, 2013, Mole, 2013).

They can accomplish this in two ways: either by providing internal promoters whose transcripts escape into neighbouring DNA (Glansdorff, et al., 1981, Simons, et al., 1983) or by hybrid promoter formation. Many IS carry -35 promoter components oriented towards the flanking DNA (Fig 1.24.1). In a number of cases this plays an important part in their transposition since a significant number of IS transpose using an excised transposon circle (Fig 1.24.1) with abutted left and right ends. For these IS, the other end carries a -10 element oriented inwards towards the Tpase gene. Together with the -35, this generates a strong promoter on formation of the circle junction to drive Tpase expression required for catalysis of integration (Fig 1.24.2) (Chandler, et al., 2015); (Ton-Hoang, et al., 1997, Perkins-Balding, et al., 1999, Duval-Valentin, et al., 2001). Thus if integration occurs next to a resident -10 sequence, the IS -35 sequence can contribute to a hybrid promoter to drive expression of neighboring genes [see (Prentki, et al., 1986)]. At present this phenomenon had been reported to occur with over 30 different IS in at least 17 bacterial species (Depardieu et al., 2007, Siguier et al., 2014) (Table 3: IS and Gene Expression). Indeed, specific vector plasmids have been designed to identify activating insertions (e.g. (Szeverenyi et al., 1996))

IS activity can affect efflux mechanisms resulting in increased resistance: IS1 or IS10 insertion can up-regulate the AcrAB-TolC pump in Salmonella enterica (Olliver et al., 2005); IS1 or IS2 insertion upstream of AcrEF (Jellen-Ritter & Kern, 2001, Kobayashi, et al., 2001) and IS186 insertional inactivation of the AcrAB repressor, AcrR, in Escherichia coli (Jellen-Ritter & Kern, 2001), all lead to increased resistance to fluoroquinolones. Insertional inactivation of specific porins can also play a significant role (Wolter, et al., 2004).

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