Difference between revisions of "General Information/IS and Gene Expression"

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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<ref><nowiki><pubmed>1101028</pubmed></nowiki></ref><ref><nowiki><pubmed>6271458</pubmed></nowiki></ref> that IS can also activate gene expression. This capacity has recently received much attention due to the increase in resistance to various antibacterials<ref><nowiki><pubmed>16952941</pubmed></nowiki></ref><ref><nowiki><pubmed>12923109</pubmed></nowiki></ref><ref><nowiki><pubmed>23158541</pubmed></nowiki></ref>, a worrying public health threat<ref><nowiki><pubmed>23887414</pubmed></nowiki></ref><ref><nowiki><pubmed>23887415</pubmed></nowiki></ref>.
 
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<ref><nowiki><pubmed>1101028</pubmed></nowiki></ref><ref><nowiki><pubmed>6271458</pubmed></nowiki></ref> that IS can also activate gene expression. This capacity has recently received much attention due to the increase in resistance to various antibacterials<ref><nowiki><pubmed>16952941</pubmed></nowiki></ref><ref><nowiki><pubmed>12923109</pubmed></nowiki></ref><ref><nowiki><pubmed>23158541</pubmed></nowiki></ref>, a worrying public health threat<ref><nowiki><pubmed>23887414</pubmed></nowiki></ref><ref><nowiki><pubmed>23887415</pubmed></nowiki></ref>.
  
−
They can accomplish this in two ways: either by providing internal promoters whose transcripts escape into neighbouring DNA<ref><nowiki><pubmed>6271458</pubmed></nowiki></ref><ref><nowiki><pubmed>6292860</pubmed></nowiki></ref><ref><nowiki><pubmed>6260746</pubmed></nowiki></ref><ref><nowiki><pubmed>6311437</pubmed></nowiki></ref> 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) <ref><nowiki><pubmed>26350305</pubmed></nowiki></ref><ref><nowiki><pubmed>9214651</pubmed></nowiki></ref><ref><nowiki><pubmed>10438765</pubmed></nowiki></ref><ref><nowiki><pubmed>11598022</pubmed></nowiki></ref>. 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 <ref><nowiki><pubmed>3029382</pubmed></nowiki></ref>]. At present this phenomenon had been reported to occur with over 30 different IS in  more than 17 bacterial species<ref><nowiki><pubmed>17223624</pubmed></nowiki></ref><ref><nowiki><pubmed>24499397</pubmed></nowiki></ref> (Table IS and Gene Expression). Indeed, specific vector plasmids have been designed to identify activating insertions (e.g. <ref><nowiki><pubmed>8863735</pubmed></nowiki></ref>).
+
They can accomplish this in two ways: either by providing internal promoters whose transcripts escape into neighboring DNA<ref><nowiki><pubmed>6271458</pubmed></nowiki></ref><ref><nowiki><pubmed>6292860</pubmed></nowiki></ref><ref><nowiki><pubmed>6260746</pubmed></nowiki></ref><ref><nowiki><pubmed>6311437</pubmed></nowiki></ref> 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) <ref><nowiki><pubmed>26350305</pubmed></nowiki></ref><ref><nowiki><pubmed>9214651</pubmed></nowiki></ref><ref><nowiki><pubmed>10438765</pubmed></nowiki></ref><ref><nowiki><pubmed>11598022</pubmed></nowiki></ref>. 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 <ref><nowiki><pubmed>3029382</pubmed></nowiki></ref>]. At present this phenomenon had been reported to occur with over 30 different IS in  more than 17 bacterial species<ref><nowiki><pubmed>17223624</pubmed></nowiki></ref><ref><nowiki><pubmed>24499397</pubmed></nowiki></ref> (Table IS and Gene Expression below). Indeed, specific vector plasmids have been designed to identify activating insertions (e.g. <ref><nowiki><pubmed>8863735</pubmed></nowiki></ref>).
  
−
{|class="wikitable" style="margin:auto"
+
IS activity can affect efflux mechanisms resulting in increased resistance: IS1 or IS10 insertion can up-regulate the AcrAB-TolC pump in ''Salmonella enterica''<ref><nowiki><pubmed>15616308</pubmed></nowiki></ref>; IS''1'' or IS''2'' insertion upstream of AcrEF<ref><nowiki><pubmed>11302812</pubmed></nowiki></ref><ref><nowiki><pubmed>11274125</pubmed></nowiki></ref> and IS''186'' insertional inactivation of the AcrAB repressor, AcrR, in ''Escherichia coli''<ref><nowiki><pubmed>11302812</pubmed></nowiki></ref>, all lead to increased resistance to fluoroquinolones. Insertional inactivation of specific porins can also play a significant role<ref><nowiki><pubmed>15212803</pubmed></nowiki></ref>.
−
|colspan="9"|Table 3. IS and gene expression.
+
 
 +
<br />
 +
 
 +
[[Image:1.24.1.png|thumb|center|510x510px|'''Fig. 1.24.1.''' Copy out paste in (DDE).|alt=]]<br />[[Image:1.24.2.png|thumb|center|510x510px|'''Fig 1.24.2.''' Promoter Activities of junction fragments from different IS circles.|alt=]]
 +
 
 +
 
 +
 
 +
IS and Gene Expression
 +
 
 +
<br />
 +
 
 +
{| class="wikitable" style="margin:auto"
 +
| colspan="9" |'''Table. IS and gene expression.'''
 
|-
 
|-
−
!scope="col"|IS family||IS name||Mechanism||Gene(s) affected||Organism||Reference||Clinical/Experimental
+
! scope="col" |IS family||IS name||Mechanism||Gene(s) affected||Organism||Reference||Clinical/Experimental
 
|-
 
|-
−
|rowspan="3"|IS<i>1</i>||rowspan="3"|IS<i>1</i>||Cointegrate||<i>Em<sup>R</sup></i>||rowspan="2"|<i>Escherichia coli</i>||<ref><nowiki><pubmed>6283551</pubmed></nowiki></ref>||C?
+
| rowspan="3" |IS<i>1</i>|| rowspan="3" |IS<i>1</i>||Cointegrate||<i>Em<sup>R</sup></i>|| rowspan="2" |<i>Escherichia coli</i>||<ref><nowiki><pubmed>6283551</pubmed></nowiki></ref>||C?
 
|-
 
|-
 
|Copy-paste circles||<i>bla<sub>TEM-1</sub></i>||<ref><nowiki><pubmed>3029382</pubmed></nowiki></ref>||E
 
|Copy-paste circles||<i>bla<sub>TEM-1</sub></i>||<ref><nowiki><pubmed>3029382</pubmed></nowiki></ref>||E
Line 14: Line 26:
 
|—||<i>acrEF</i> pump||<i>Salmonella enterica</i>||<ref><nowiki><pubmed>15616308</pubmed></nowiki></ref>||E
 
|—||<i>acrEF</i> pump||<i>Salmonella enterica</i>||<ref><nowiki><pubmed>15616308</pubmed></nowiki></ref>||E
 
|-
 
|-
−
|rowspan="12"|IS<i>3</i>||rowspan="6"|IS<i>2</i>||rowspan="6"|Copy-paste circles||<i>gal</i>||rowspan="6"|<i>Escherichia coli</i>||<ref><nowiki><pubmed>4610339</pubmed></nowiki></ref><ref><nowiki><pubmed>339095</pubmed></nowiki></ref>||E
+
| rowspan="12" |IS<i>3</i>|| rowspan="6" |IS<i>2</i>|| rowspan="6" |Copy-paste circles||<i>gal</i>|| rowspan="6" |<i>Escherichia coli</i>||<ref><nowiki><pubmed>4610339</pubmed></nowiki></ref><ref><nowiki><pubmed>339095</pubmed></nowiki></ref>||E
 
|-
 
|-
 
|<i>gal</i>|||<ref><nowiki><pubmed>6283551</pubmed></nowiki></ref><ref><nowiki><pubmed>6271458</pubmed></nowiki></ref>||E
 
|<i>gal</i>|||<ref><nowiki><pubmed>6283551</pubmed></nowiki></ref><ref><nowiki><pubmed>6271458</pubmed></nowiki></ref>||E
 
|-
 
|-
−
|<i>argE</i>||rowspan="4"|<ref><nowiki><pubmed>6187472</pubmed></nowiki></ref><ref><nowiki><pubmed>11302812</pubmed></nowiki></ref>||E
+
|<i>argE</i>|| rowspan="4" |<ref><nowiki><pubmed>6187472</pubmed></nowiki></ref><ref><nowiki><pubmed>11302812</pubmed></nowiki></ref>||E
 
|-
 
|-
 
|<i>Em<sup>R</sup></i>||C?
 
|<i>Em<sup>R</sup></i>||C?
Line 26: Line 38:
 
|<i>acrEF</i> pump||E
 
|<i>acrEF</i> pump||E
 
|-
 
|-
−
|rowspan="3"|IS<i>3</i>||rowspan="3"|Copy-paste circles||<i>argE</i>||rowspan="3"|<i>Escherichia coli</i>||<ref><nowiki><pubmed>6271458</pubmed></nowiki></ref>||E
+
| rowspan="3" |IS<i>3</i>|| rowspan="3" |Copy-paste circles||<i>argE</i>|| rowspan="3" |<i>Escherichia coli</i>||<ref><nowiki><pubmed>6271458</pubmed></nowiki></ref>||E
 
|-
 
|-
 
|<i>argE</i>||<ref><nowiki><pubmed>6292860</pubmed></nowiki></ref>||E
 
|<i>argE</i>||<ref><nowiki><pubmed>6292860</pubmed></nowiki></ref>||E
Line 38: Line 50:
 
|IS<i>Kpn8</i>||Copy-paste circles||<i>blaKCP-2</i>||<i>Escherichia coli</i>, <i>Citrobacter freundii</i>, <i>Enterobacter cloacae</i>, <i>Enterobacter aerogenes</i>, and <i>Klebsiella oxytoca||<ref><nowiki><pubmed>24433026</pubmed></nowiki></ref>||C
 
|IS<i>Kpn8</i>||Copy-paste circles||<i>blaKCP-2</i>||<i>Escherichia coli</i>, <i>Citrobacter freundii</i>, <i>Enterobacter cloacae</i>, <i>Enterobacter aerogenes</i>, and <i>Klebsiella oxytoca||<ref><nowiki><pubmed>24433026</pubmed></nowiki></ref>||C
 
|-
 
|-
−
|rowspan="9"|IS<i>4</i>||rowspan="3"|IS<i>10</i>||Cut-paste (hairpin)||<i>his</i>||<i>Salmonella typhimurium</i>||<ref><nowiki><pubmed>6289329</pubmed></nowiki></ref>||E
+
| rowspan="9" |IS<i>4</i>|| rowspan="3" |IS<i>10</i>||Cut-paste (hairpin)||<i>his</i>||<i>Salmonella typhimurium</i>||<ref><nowiki><pubmed>6289329</pubmed></nowiki></ref>||E
 
|-
 
|-
 
|Cut-paste||—||<i>Escherichia coli</i>||<ref><nowiki><pubmed>6311437</pubmed></nowiki></ref>||E
 
|Cut-paste||—||<i>Escherichia coli</i>||<ref><nowiki><pubmed>6311437</pubmed></nowiki></ref>||E
Line 46: Line 58:
 
|IS<i>50</i>||Cut-paste (hairpin)||<i>aph3’II</i>||<i>Escherichia coli</i>||<ref><nowiki><pubmed>6260374</pubmed></nowiki></ref>||E
 
|IS<i>50</i>||Cut-paste (hairpin)||<i>aph3’II</i>||<i>Escherichia coli</i>||<ref><nowiki><pubmed>6260374</pubmed></nowiki></ref>||E
 
|-
 
|-
−
|rowspan="2"|IS<i>1999</i>||rowspan="2"|—||<i>bla<sub>VEB-1</sub></i>||<i>Pseudomonas aeruginosa</i>||<ref><nowiki><pubmed>12923109</pubmed></nowiki></ref>||C
+
| rowspan="2" |IS<i>1999</i>|| rowspan="2" |—||<i>bla<sub>VEB-1</sub></i>||<i>Pseudomonas aeruginosa</i>||<ref><nowiki><pubmed>12923109</pubmed></nowiki></ref>||C
 
|-
 
|-
 
|<i>bla<sub>VEB-1</sub></i>/<i>bla<sub>OXA-48</sub></i>||<i>Escherichia coli</i>||<ref><nowiki><pubmed>16952941</pubmed></nowiki></ref>||C
 
|<i>bla<sub>VEB-1</sub></i>/<i>bla<sub>OXA-48</sub></i>||<i>Escherichia coli</i>||<ref><nowiki><pubmed>16952941</pubmed></nowiki></ref>||C
Line 52: Line 64:
 
|IS<i>Pa12</i>||—||<i>blaPER-1</i>||<i>Salmonella enterica</i>, <i>Pseudomonas aeruginosa</i>, <i>Providencia stuartii</i>, <i>Acinetobacter baumannii</i>||<ref><nowiki><pubmed>12936998</pubmed></nowiki></ref>||C
 
|IS<i>Pa12</i>||—||<i>blaPER-1</i>||<i>Salmonella enterica</i>, <i>Pseudomonas aeruginosa</i>, <i>Providencia stuartii</i>, <i>Acinetobacter baumannii</i>||<ref><nowiki><pubmed>12936998</pubmed></nowiki></ref>||C
 
|-
 
|-
−
|rowspan="2"|IS<i>Aba1</i>||rowspan="2"|—||<i>bla<sub>ampC</sub></i>||rowspan="2"|<i>Acinetobacter baumannii</i>||<ref><nowiki><pubmed>12951337</pubmed></nowiki></ref><ref><nowiki><pubmed>14742218</pubmed></nowiki></ref><ref><nowiki><pubmed>16441449</pubmed></nowiki></ref>||C
+
| rowspan="2" |IS<i>Aba1</i>|| rowspan="2" |—||<i>bla<sub>ampC</sub></i>|| rowspan="2" |<i>Acinetobacter baumannii</i>||<ref><nowiki><pubmed>12951337</pubmed></nowiki></ref><ref><nowiki><pubmed>14742218</pubmed></nowiki></ref><ref><nowiki><pubmed>16441449</pubmed></nowiki></ref>||C
 
|-
 
|-
 
|<i>bla<sub>OXA-51</sub></i>/<i>bla<sub>OXA-23</sub></i>||<ref><nowiki><pubmed>16630258</pubmed></nowiki></ref>||C
 
|<i>bla<sub>OXA-51</sub></i>/<i>bla<sub>OXA-23</sub></i>||<ref><nowiki><pubmed>16630258</pubmed></nowiki></ref>||C
 
|-
 
|-
−
|rowspan="6"|IS<i>5</i>
+
| rowspan="6" |IS<i>5</i>
−
|IS<i>5</i>||rowspan="6"|—||<i>EmR</i>||<i>Escherichia coli</i>||<ref><nowiki><pubmed>6283551</pubmed></nowiki></ref>||C?
+
|IS<i>5</i>|| rowspan="6" |—||<i>EmR</i>||<i>Escherichia coli</i>||<ref><nowiki><pubmed>6283551</pubmed></nowiki></ref>||C?
 
|-
 
|-
 
|ISFtu2||general||<i>Francisella tularensis</i>||<ref><nowiki><pubmed>19749055</pubmed></nowiki></ref>||Natural isolate
 
|ISFtu2||general||<i>Francisella tularensis</i>||<ref><nowiki><pubmed>19749055</pubmed></nowiki></ref>||Natural isolate
Line 69: Line 81:
 
|IS<i>402</i>||<i>bla</i>||<i>Pseudomonas cepacia</i>||<ref><nowiki><pubmed>3025189</pubmed></nowiki></ref>||E
 
|IS<i>402</i>||<i>bla</i>||<i>Pseudomonas cepacia</i>||<ref><nowiki><pubmed>3025189</pubmed></nowiki></ref>||E
 
|-
 
|-
−
|rowspan="6"|IS<i>6</i>
+
| rowspan="6" |IS<i>6</i>
−
|IS<i>257</i>||Cointegrate||<i>dfrA</i>||<i>Staphylococcus aureus</i>||<ref><nowiki><pubmed>7840551</pubmed></nowiki></ref>||rowspan="6"|C
+
|IS<i>257</i>||Cointegrate||<i>dfrA</i>||<i>Staphylococcus aureus</i>||<ref><nowiki><pubmed>7840551</pubmed></nowiki></ref>|| rowspan="6" |C
 
|-
 
|-
 
|IS<i>257</i>||Cointegrate||<i>tet</i>||<i>Staphylococcus aureus</i>||<ref><nowiki><pubmed>10852863</pubmed></nowiki></ref>
 
|IS<i>257</i>||Cointegrate||<i>tet</i>||<i>Staphylococcus aureus</i>||<ref><nowiki><pubmed>10852863</pubmed></nowiki></ref>
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|IS<i>1008</i>||—||<i>bla<sub>OXA-58</sub></i>||<i>Acinetobacter baumannii</i>||<ref><nowiki><pubmed>18443121</pubmed></nowiki></ref>
 
|IS<i>1008</i>||—||<i>bla<sub>OXA-58</sub></i>||<i>Acinetobacter baumannii</i>||<ref><nowiki><pubmed>18443121</pubmed></nowiki></ref>
 
|-
 
|-
−
|rowspan="2"|IS<i>26</i>||rowspan="2"|—||<i>aphA7</i>, <i>bla<sub>S2A</sub></i>||<i>Klebsiella pneumoniae</i>||<ref><nowiki><pubmed>2160941</pubmed></nowiki></ref>
+
| rowspan="2" |IS<i>26</i>|| rowspan="2" |—||<i>aphA7</i>, <i>bla<sub>S2A</sub></i>||<i>Klebsiella pneumoniae</i>||<ref><nowiki><pubmed>2160941</pubmed></nowiki></ref>
 
|-
 
|-
 
|<i>bla<sub>SHV-2a</sub></i>||<i>Pseudomonas aeruginosa</i>||<ref><nowiki><pubmed>10223953</pubmed></nowiki></ref>
 
|<i>bla<sub>SHV-2a</sub></i>||<i>Pseudomonas aeruginosa</i>||<ref><nowiki><pubmed>10223953</pubmed></nowiki></ref>
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|IS<i>140</i>||—||<i>aac(3)</i>-III and -IV||—||<ref><nowiki><pubmed>6318050</pubmed></nowiki></ref>
 
|IS<i>140</i>||—||<i>aac(3)</i>-III and -IV||—||<ref><nowiki><pubmed>6318050</pubmed></nowiki></ref>
 
|-
 
|-
−
|rowspan="2"|IS<i>21</i>
+
| rowspan="2" |IS<i>21</i>
−
|IS<i>Bf1</i>||rowspan="2"|Copy-paste circle||<i>cepA</i>||<i>Bacteroides fragilis</i>||<ref><nowiki><pubmed>7517394</pubmed></nowiki></ref>||rowspan="2"|C
+
|IS<i>Bf1</i>|| rowspan="2" |Copy-paste circle||<i>cepA</i>||<i>Bacteroides fragilis</i>||<ref><nowiki><pubmed>7517394</pubmed></nowiki></ref>|| rowspan="2" |C
 
|-
 
|-
 
|IS<i>Kpn7</i>||<i>blaKPC</i>||<i>Klebsiellea pneumonia</i>||<ref><nowiki><pubmed>18227185</pubmed></nowiki></ref>
 
|IS<i>Kpn7</i>||<i>blaKPC</i>||<i>Klebsiellea pneumonia</i>||<ref><nowiki><pubmed>18227185</pubmed></nowiki></ref>
 
|-
 
|-
−
|rowspan="6"|IS<i>30</i>
+
| rowspan="6" |IS<i>30</i>
−
|IS<i>30</i>||rowspan="6"|Copy-paste circle||<i>galK</i>||<i>Escherichia coli</i>||<ref><nowiki><pubmed>3039299</pubmed></nowiki></ref>||E
+
|IS<i>30</i>|| rowspan="6" |Copy-paste circle||<i>galK</i>||<i>Escherichia coli</i>||<ref><nowiki><pubmed>3039299</pubmed></nowiki></ref>||E
 
|-
 
|-
−
|rowspan="2"|IS<i>18</i>||<i>aac(6’)-Ij</i>||rowspan="2"|<i>Acinetobacter</i> sp.||<ref><nowiki><pubmed>9756793</pubmed></nowiki></ref>||rowspan="2"|C
+
| rowspan="2" |IS<i>18</i>||<i>aac(6’)-Ij</i>|| rowspan="2" |<i>Acinetobacter</i> sp.||<ref><nowiki><pubmed>9756793</pubmed></nowiki></ref>|| rowspan="2" |C
 
|-
 
|-
 
|<i>blaOXA257</i>||<ref><nowiki><pubmed>23014718</pubmed></nowiki></ref>
 
|<i>blaOXA257</i>||<ref><nowiki><pubmed>23014718</pubmed></nowiki></ref>
 
|-
 
|-
−
|rowspan="2"|IS<i>4351</i>||<i>ermF</i>||rowspan="2"|<i>Bacteroides fragilis</i>||<ref><nowiki><pubmed>3038844</pubmed></nowiki></ref>||rowspan="2"|C
+
| rowspan="2" |IS<i>4351</i>||<i>ermF</i>|| rowspan="2" |<i>Bacteroides fragilis</i>||<ref><nowiki><pubmed>3038844</pubmed></nowiki></ref>|| rowspan="2" |C
 
|-
 
|-
 
|<i>cfiA</i>||<ref><nowiki><pubmed>23158541</pubmed></nowiki></ref>
 
|<i>cfiA</i>||<ref><nowiki><pubmed>23158541</pubmed></nowiki></ref>
 
|-
 
|-
−
|IS<i>1086</i>||<i>cnrCBAT</i> (Zn<sup>R</sup>)||<i>Cupriavidus metallidurans</i>||||E
+
|IS<i>1086</i>||<i>cnrCBAT</i> (Zn<sup>R</sup>)||<i>Cupriavidus metallidurans</i>|| ||E
 
|-
 
|-
−
|rowspan="4"|IS<i>256</i>
+
| rowspan="4" |IS<i>256</i>
−
|rowspan="2"|IS<i>256</i>||rowspan="4"|Copy-paste circles||<i>mecA</i>||<i>Staphylococcus sciuri</i>||rowspan="2"|<ref><nowiki><pubmed>9371438</pubmed></nowiki></ref><ref><nowiki><pubmed>12511511</pubmed></nowiki></ref>||rowspan="2"|—
+
| rowspan="2" |IS<i>256</i>|| rowspan="4" |Copy-paste circles||<i>mecA</i>||<i>Staphylococcus sciuri</i>|| rowspan="2" |<ref><nowiki><pubmed>9371438</pubmed></nowiki></ref><ref><nowiki><pubmed>12511511</pubmed></nowiki></ref>|| rowspan="2" |—
 
|-
 
|-
 
|<i>llm</i>||<i>Staphylococcus aureus</i>
 
|<i>llm</i>||<i>Staphylococcus aureus</i>
Line 109: Line 121:
 
|IS<i>406</i>||—||<i>Burkholderia cepacia</i>||<ref><nowiki><pubmed>3025189</pubmed></nowiki></ref>||E
 
|IS<i>406</i>||—||<i>Burkholderia cepacia</i>||<ref><nowiki><pubmed>3025189</pubmed></nowiki></ref>||E
 
|-
 
|-
−
|rowspan="2"|IS<i>481</i>||IS<i>481</i>||rowspan="2"|Copy-paste circles||<i>katA</i>||<i>Bordetella pertussis</i>||<ref><nowiki><pubmed>7830550</pubmed></nowiki></ref>||—
+
| rowspan="2" |IS<i>481</i>||IS<i>481</i>|| rowspan="2" |Copy-paste circles||<i>katA</i>||<i>Bordetella pertussis</i>||<ref><nowiki><pubmed>7830550</pubmed></nowiki></ref>||—
 
|-
 
|-
 
|IS<i>Rme5</i>||<i>cnrCBAT</i> (Zn R)||<i>Cupriavidus metallidurans</i>||<ref><nowiki><pubmed>27047473</pubmed></nowiki></ref>||E
 
|IS<i>Rme5</i>||<i>cnrCBAT</i> (Zn R)||<i>Cupriavidus metallidurans</i>||<ref><nowiki><pubmed>27047473</pubmed></nowiki></ref>||E
Line 115: Line 127:
 
|IS<i>630</i>||IS<i>Ftu1</i>||Tc-like||general||<i>Francisella tularensis</i>||<ref><nowiki><pubmed>19749055</pubmed></nowiki></ref>||Natural isolate
 
|IS<i>630</i>||IS<i>Ftu1</i>||Tc-like||general||<i>Francisella tularensis</i>||<ref><nowiki><pubmed>19749055</pubmed></nowiki></ref>||Natural isolate
 
|-
 
|-
−
|rowspan="3"|IS<i>982</i>
+
| rowspan="3" |IS<i>982</i>
−
|rowspan="2"|IS<i>1187</i>||rowspan="3"|—||rowspan="2"|<i>cfiA</i>||rowspan="2"|<i>Bacteroides fragilis</i>||<ref><nowiki><pubmed>8057831</pubmed></nowiki></ref>||E+C
+
| rowspan="2" |IS<i>1187</i>|| rowspan="3" |—|| rowspan="2" |<i>cfiA</i>|| rowspan="2" |<i>Bacteroides fragilis</i>||<ref><nowiki><pubmed>8057831</pubmed></nowiki></ref>||E+C
 
|-
 
|-
 
|<ref><nowiki><pubmed>23158541</pubmed></nowiki></ref><ref><nowiki><pubmed>11344163</pubmed></nowiki></ref><ref><nowiki><pubmed>12604530</pubmed></nowiki></ref>||C
 
|<ref><nowiki><pubmed>23158541</pubmed></nowiki></ref><ref><nowiki><pubmed>11344163</pubmed></nowiki></ref><ref><nowiki><pubmed>12604530</pubmed></nowiki></ref>||C
Line 122: Line 134:
 
|IS<i>982</i>||<i>citQRP</i>||<i>Lactococcus lactis</i>||<ref><nowiki><pubmed>8602160</pubmed></nowiki></ref>||—
 
|IS<i>982</i>||<i>citQRP</i>||<i>Lactococcus lactis</i>||<ref><nowiki><pubmed>8602160</pubmed></nowiki></ref>||—
 
|-
 
|-
−
|rowspan="12"|IS<i>1380</i>
+
| rowspan="12" |IS<i>1380</i>
−
|IS<i>Bf12</i>||rowspan="12"|—||rowspan="6"|<i>cfiA</i>||rowspan="6"|<i>Bacteroides fragilis</i>||<ref><nowiki><pubmed>23158541</pubmed></nowiki></ref>||rowspan="12"|C
+
|IS<i>Bf12</i>|| rowspan="12" |—|| rowspan="6" |<i>cfiA</i>|| rowspan="6" |<i>Bacteroides fragilis</i>||<ref><nowiki><pubmed>23158541</pubmed></nowiki></ref>|| rowspan="12" |C
 
|-
 
|-
 
|IS<i>612</i>||<ref><nowiki><pubmed>12604530</pubmed></nowiki></ref>
 
|IS<i>612</i>||<ref><nowiki><pubmed>12604530</pubmed></nowiki></ref>
Line 135: Line 147:
 
|IS<i>942</i>||<ref><nowiki><pubmed>11344163</pubmed></nowiki></ref>
 
|IS<i>942</i>||<ref><nowiki><pubmed>11344163</pubmed></nowiki></ref>
 
|-
 
|-
−
|rowspan="5"|IS<i>Ecp1</i>||<i>bla<sub>CTX-M-15</sub></i>||Enterobacteriaceae||<ref><nowiki><pubmed>11470367</pubmed></nowiki></ref>
+
| rowspan="5" |IS<i>Ecp1</i>||<i>bla<sub>CTX-M-15</sub></i>||Enterobacteriaceae||<ref><nowiki><pubmed>11470367</pubmed></nowiki></ref>
 
|-
 
|-
 
|<i>bla<sub>CTX-M-17</sub></i>||<i>Klebsiella pneumoniae</i>||<ref><nowiki><pubmed>12435670</pubmed></nowiki></ref>
 
|<i>bla<sub>CTX-M-17</sub></i>||<i>Klebsiella pneumoniae</i>||<ref><nowiki><pubmed>12435670</pubmed></nowiki></ref>
Line 147: Line 159:
 
|IS<i>1187</i>||<i>cfiA</i>||<i>Bacteroides fragilis</i>||<ref><nowiki><pubmed>11344163</pubmed></nowiki></ref>
 
|IS<i>1187</i>||<i>cfiA</i>||<i>Bacteroides fragilis</i>||<ref><nowiki><pubmed>11344163</pubmed></nowiki></ref>
 
|-
 
|-
−
|rowspan="2"|IS<i>L3</i>
+
| rowspan="2" |IS<i>L3</i>
−
|IS<i>Sg1</i>||rowspan="2"|Copy-paste circles||<i>sspB</i> (surface antigen)||<i>Streptococcus gordonii</i>||<ref><nowiki><pubmed>9202480</pubmed></nowiki></ref>||rowspan="2"|—
+
|IS<i>Sg1</i>|| rowspan="2" |Copy-paste circles||<i>sspB</i> (surface antigen)||<i>Streptococcus gordonii</i>||<ref><nowiki><pubmed>9202480</pubmed></nowiki></ref>|| rowspan="2" |—
 
|-
 
|-
 
|IS<i>1411</i>||<i>pheBA</i>||<i>Pseudomonas putida</i>||<ref><nowiki><pubmed>9765560</pubmed></nowiki></ref>
 
|IS<i>1411</i>||<i>pheBA</i>||<i>Pseudomonas putida</i>||<ref><nowiki><pubmed>9765560</pubmed></nowiki></ref>
 
|-
 
|-
−
|rowspan="2"|IS<i>As1</i>
+
| rowspan="2" |IS<i>As1</i>
−
|IS<i>1548</i>||rowspan="2"|—||<i>lmb</i> (lamelin binding)||<i>Streptococcus agalactiae</i>||<ref><nowiki><pubmed>20520730</pubmed></nowiki></ref>||—
+
|IS<i>1548</i>|| rowspan="2" |—||<i>lmb</i> (lamelin binding)||<i>Streptococcus agalactiae</i>||<ref><nowiki><pubmed>20520730</pubmed></nowiki></ref>||—
 
|-
 
|-
 
|nd||—||<i>Acinetobacter baumannii</i>||<ref><nowiki><pubmed>12951337</pubmed></nowiki></ref>||C
 
|nd||—||<i>Acinetobacter baumannii</i>||<ref><nowiki><pubmed>12951337</pubmed></nowiki></ref>||C
 
|-
 
|-
−
|rowspan="3"|IS<i>NYC</i>
+
| rowspan="3" |IS<i>NYC</i>
−
|IS<i>403</i>||rowspan="3"|—||rowspan="3"|bla||rowspan="3"|<i>Burkholderia cepacia</i>||rowspan="3"|<ref><nowiki><pubmed>3025189</pubmed></nowiki></ref>||rowspan="3"|E
+
|IS<i>403</i>|| rowspan="3" |—|| rowspan="3" |bla|| rowspan="3" |<i>Burkholderia cepacia</i>|| rowspan="3" |<ref><nowiki><pubmed>3025189</pubmed></nowiki></ref>|| rowspan="3" |E
 
|-
 
|-
 
|IS<i>404</i>
 
|IS<i>404</i>
Line 165: Line 177:
 
|}
 
|}
  
−
 
−
IS activity can affect efflux mechanisms resulting in increased resistance: IS1 or IS10 insertion can up-regulate the AcrAB-TolC pump in Salmonella enterica<ref><nowiki><pubmed>15616308</pubmed></nowiki></ref>; IS1 or IS2 insertion upstream of AcrEF<ref><nowiki><pubmed>11302812</pubmed></nowiki></ref><ref><nowiki><pubmed>11274125</pubmed></nowiki></ref> and IS186 insertional inactivation of the AcrAB repressor, AcrR, in Escherichia coli<ref><nowiki><pubmed>11302812</pubmed></nowiki></ref>, all lead to increased resistance to fluoroquinolones. Insertional inactivation of specific porins can also play a significant role<ref><nowiki><pubmed>15212803</pubmed></nowiki></ref>.
 
−
 
−
[[Image:1.24.1.png|thumb|center|600px|Fig 1.24.1]]
 
−
[[Image:1.24.2.png|thumb|center|600px|Fig 1.24.2]]
 
  
 
==Bibliography==
 
==Bibliography==
−
<references/>
+
<references />

Revision as of 18:52, 30 April 2020

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[1][2] that IS can also activate gene expression. This capacity has recently received much attention due to the increase in resistance to various antibacterials[3][4][5], a worrying public health threat[6][7].

They can accomplish this in two ways: either by providing internal promoters whose transcripts escape into neighboring DNA[8][9][10][11] 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) [12][13][14][15]. 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 [16]]. At present this phenomenon had been reported to occur with over 30 different IS in more than 17 bacterial species[17][18] (Table IS and Gene Expression below). Indeed, specific vector plasmids have been designed to identify activating insertions (e.g. [19]).

IS activity can affect efflux mechanisms resulting in increased resistance: IS1 or IS10 insertion can up-regulate the AcrAB-TolC pump in Salmonella enterica[20]; IS1 or IS2 insertion upstream of AcrEF[21][22] and IS186 insertional inactivation of the AcrAB repressor, AcrR, in Escherichia coli[23], all lead to increased resistance to fluoroquinolones. Insertional inactivation of specific porins can also play a significant role[24].


Fig. 1.24.1. Copy out paste in (DDE).


Fig 1.24.2. Promoter Activities of junction fragments from different IS circles.


IS and Gene Expression


Table. IS and gene expression.
IS family IS name Mechanism Gene(s) affected Organism Reference Clinical/Experimental
IS1 IS1 Cointegrate EmR Escherichia coli [25] C?
Copy-paste circles blaTEM-1 [26] E
— acrEF pump Salmonella enterica [27] E
IS3 IS2 Copy-paste circles gal Escherichia coli [28][29] E
gal [30][31] E
argE [32][33] E
EmR C?
blaampC E
acrEF pump E
IS3 Copy-paste circles argE Escherichia coli [34] E
argE [35] E
citT [36] E
IS981 Copy-paste circles ldhB Lactococcus lactis [37] E
IS6110 Copy-paste circles Rv2280 and PE-PGRS gene, Rv1468c Mycobacterium tuberculosis [38] E
ISKpn8 Copy-paste circles blaKCP-2 Escherichia coli, Citrobacter freundii, Enterobacter cloacae, Enterobacter aerogenes, and Klebsiella oxytoca [39] C
IS4 IS10 Cut-paste (hairpin) his Salmonella typhimurium [40] E
Cut-paste — Escherichia coli [41] E
Cut-paste acrEF pump Salmonella enterica [42] E
IS50 Cut-paste (hairpin) aph3’II Escherichia coli [43] E
IS1999 — blaVEB-1 Pseudomonas aeruginosa [44] C
blaVEB-1/blaOXA-48 Escherichia coli [45] C
ISPa12 — blaPER-1 Salmonella enterica, Pseudomonas aeruginosa, Providencia stuartii, Acinetobacter baumannii [46] C
ISAba1 — blaampC Acinetobacter baumannii [47][48][49] C
blaOXA-51/blaOXA-23 [50] C
IS5 IS5 — EmR Escherichia coli [51] C?
ISFtu2 general Francisella tularensis [52] Natural isolate
ISVa1 (iron uptake) Vibrio anguilarum [53] Natural isolate
IS1168 (IS1186) nimA, nimB Bacteroides sp. [54] C
IS1186 cfiA Bacteroides fragilis [55][56] C
IS402 bla Pseudomonas cepacia [57] E
IS6 IS257 Cointegrate dfrA Staphylococcus aureus [58] C
IS257 Cointegrate tet Staphylococcus aureus [59]
IS1008 — blaOXA-58 Acinetobacter baumannii [60]
IS26 — aphA7, blaS2A Klebsiella pneumoniae [61]
blaSHV-2a Pseudomonas aeruginosa [62]
IS140 — aac(3)-III and -IV — [63]
IS21 ISBf1 Copy-paste circle cepA Bacteroides fragilis [64] C
ISKpn7 blaKPC Klebsiellea pneumonia [65]
IS30 IS30 Copy-paste circle galK Escherichia coli [66] E
IS18 aac(6’)-Ij Acinetobacter sp. [67] C
blaOXA257 [68]
IS4351 ermF Bacteroides fragilis [69] C
cfiA [70]
IS1086 cnrCBAT (ZnR) Cupriavidus metallidurans E
IS256 IS256 Copy-paste circles mecA Staphylococcus sciuri [71][72] —
llm Staphylococcus aureus
IS1490 — Burkholderia cepacia [73] —
IS406 — Burkholderia cepacia [74] E
IS481 IS481 Copy-paste circles katA Bordetella pertussis [75] —
ISRme5 cnrCBAT (Zn R) Cupriavidus metallidurans [76] E
IS630 ISFtu1 Tc-like general Francisella tularensis [77] Natural isolate
IS982 IS1187 — cfiA Bacteroides fragilis [78] E+C
[79][80][81] C
IS982 citQRP Lactococcus lactis [82] —
IS1380 ISBf12 — cfiA Bacteroides fragilis [83] C
IS612 [84]
IS613 [85]
IS614 [86][87][88]
IS1188 [89]
IS942 [90]
ISEcp1 blaCTX-M-15 Enterobacteriaceae [91]
blaCTX-M-17 Klebsiella pneumoniae [92]
blaCTX-M-19 Klebsiella pneumoniae [93]
blaCTX-M Kluyvera ascorbata [94]
rmtC Escherichia coli [95]
IS1187 cfiA Bacteroides fragilis [96]
ISL3 ISSg1 Copy-paste circles sspB (surface antigen) Streptococcus gordonii [97] —
IS1411 pheBA Pseudomonas putida [98]
ISAs1 IS1548 — lmb (lamelin binding) Streptococcus agalactiae [99] —
nd — Acinetobacter baumannii [100] C
ISNYC IS403 — bla Burkholderia cepacia [101] E
IS404
IS405


Bibliography

  1. ↑ <pubmed>1101028</pubmed>
  2. ↑ <pubmed>6271458</pubmed>
  3. ↑ <pubmed>16952941</pubmed>
  4. ↑ <pubmed>12923109</pubmed>
  5. ↑ <pubmed>23158541</pubmed>
  6. ↑ <pubmed>23887414</pubmed>
  7. ↑ <pubmed>23887415</pubmed>
  8. ↑ <pubmed>6271458</pubmed>
  9. ↑ <pubmed>6292860</pubmed>
  10. ↑ <pubmed>6260746</pubmed>
  11. ↑ <pubmed>6311437</pubmed>
  12. ↑ <pubmed>26350305</pubmed>
  13. ↑ <pubmed>9214651</pubmed>
  14. ↑ <pubmed>10438765</pubmed>
  15. ↑ <pubmed>11598022</pubmed>
  16. ↑ <pubmed>3029382</pubmed>
  17. ↑ <pubmed>17223624</pubmed>
  18. ↑ <pubmed>24499397</pubmed>
  19. ↑ <pubmed>8863735</pubmed>
  20. ↑ <pubmed>15616308</pubmed>
  21. ↑ <pubmed>11302812</pubmed>
  22. ↑ <pubmed>11274125</pubmed>
  23. ↑ <pubmed>11302812</pubmed>
  24. ↑ <pubmed>15212803</pubmed>
  25. ↑ <pubmed>6283551</pubmed>
  26. ↑ <pubmed>3029382</pubmed>
  27. ↑ <pubmed>15616308</pubmed>
  28. ↑ <pubmed>4610339</pubmed>
  29. ↑ <pubmed>339095</pubmed>
  30. ↑ <pubmed>6283551</pubmed>
  31. ↑ <pubmed>6271458</pubmed>
  32. ↑ <pubmed>6187472</pubmed>
  33. ↑ <pubmed>11302812</pubmed>
  34. ↑ <pubmed>6271458</pubmed>
  35. ↑ <pubmed>6292860</pubmed>
  36. ↑ <pubmed>22992527</pubmed>
  37. ↑ <pubmed>12867459</pubmed>
  38. ↑ <pubmed>15130120</pubmed>
  39. ↑ <pubmed>24433026</pubmed>
  40. ↑ <pubmed>6289329</pubmed>
  41. ↑ <pubmed>6311437</pubmed>
  42. ↑ <pubmed>15616308</pubmed>
  43. ↑ <pubmed>6260374</pubmed>
  44. ↑ <pubmed>12923109</pubmed>
  45. ↑ <pubmed>16952941</pubmed>
  46. ↑ <pubmed>12936998</pubmed>
  47. ↑ <pubmed>12951337</pubmed>
  48. ↑ <pubmed>14742218</pubmed>
  49. ↑ <pubmed>16441449</pubmed>
  50. ↑ <pubmed>16630258</pubmed>
  51. ↑ <pubmed>6283551</pubmed>
  52. ↑ <pubmed>19749055</pubmed>
  53. ↑ <pubmed>7568465</pubmed>
  54. ↑ <pubmed>8067736</pubmed>
  55. ↑ <pubmed>8057831</pubmed>
  56. ↑ <pubmed>7545155</pubmed>
  57. ↑ <pubmed>3025189</pubmed>
  58. ↑ <pubmed>7840551</pubmed>
  59. ↑ <pubmed>10852863</pubmed>
  60. ↑ <pubmed>18443121</pubmed>
  61. ↑ <pubmed>2160941</pubmed>
  62. ↑ <pubmed>10223953</pubmed>
  63. ↑ <pubmed>6318050</pubmed>
  64. ↑ <pubmed>7517394</pubmed>
  65. ↑ <pubmed>18227185</pubmed>
  66. ↑ <pubmed>3039299</pubmed>
  67. ↑ <pubmed>9756793</pubmed>
  68. ↑ <pubmed>23014718</pubmed>
  69. ↑ <pubmed>3038844</pubmed>
  70. ↑ <pubmed>23158541</pubmed>
  71. ↑ <pubmed>9371438</pubmed>
  72. ↑ <pubmed>12511511</pubmed>
  73. ↑ <pubmed>9098071</pubmed>
  74. ↑ <pubmed>3025189</pubmed>
  75. ↑ <pubmed>7830550</pubmed>
  76. ↑ <pubmed>27047473</pubmed>
  77. ↑ <pubmed>19749055</pubmed>
  78. ↑ <pubmed>8057831</pubmed>
  79. ↑ <pubmed>23158541</pubmed>
  80. ↑ <pubmed>11344163</pubmed>
  81. ↑ <pubmed>12604530</pubmed>
  82. ↑ <pubmed>8602160</pubmed>
  83. ↑ <pubmed>23158541</pubmed>
  84. ↑ <pubmed>12604530</pubmed>
  85. ↑ <pubmed>12604530</pubmed>
  86. ↑ <pubmed>23158541</pubmed>
  87. ↑ <pubmed>12604530</pubmed>
  88. ↑ <pubmed>19744834</pubmed>
  89. ↑ <pubmed>11344163</pubmed>
  90. ↑ <pubmed>11344163</pubmed>
  91. ↑ <pubmed>11470367</pubmed>
  92. ↑ <pubmed>12435670</pubmed>
  93. ↑ <pubmed>12936998</pubmed>
  94. ↑ <pubmed>16569841</pubmed>
  95. ↑ <pubmed>16940134</pubmed>
  96. ↑ <pubmed>11344163</pubmed>
  97. ↑ <pubmed>9202480</pubmed>
  98. ↑ <pubmed>9765560</pubmed>
  99. ↑ <pubmed>20520730</pubmed>
  100. ↑ <pubmed>12951337</pubmed>
  101. ↑ <pubmed>3025189</pubmed>
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