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).
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
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
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
& Kern, 2001), all
lead to increased resistance
to fluoroquinolones. Insertional
inactivation of specific porins can also play a significant role (Wolter, et al.,
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