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Decrypting the H-NS-dependent regulatory cascade of acid stress resistance in Escherichia coli.

Krin E, Danchin A, Soutourina O - BMC Microbiol. (2010)

Bottom Line: RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways plays a central role in the regulatory cascade.Finally, we found that in addition to H-NS and RcsB, a third regulator, HdfR, inversely controls glutamate-dependent acid resistance pathway and motility.H-NS lies near the top of the hierarchy orchestrating acid response centred on RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways.

View Article: PubMed Central - HTML - PubMed

Affiliation: Unité de Plasticité du Génome Bactérien, Institut Pasteur, France. ekrin@pasteur.fr

ABSTRACT

Background: H-NS regulates the acid stress resistance. The present study aimed to characterize the H-NS-dependent cascade governing the acid stress resistance pathways and to define the interplay between the different regulators.

Results: We combined mutational, phenotypic and gene expression analyses, to unravel the regulatory hierarchy in acid resistance involving H-NS, RcsB-P/GadE complex, HdfR, CadC, AdiY regulators, and DNA-binding assays to separate direct effects from indirect ones. RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways plays a central role in the regulatory cascade. However, H-NS also directly controls specific regulators of these pathways (e.g. cadC) and genes involved in general stress resistance (hdeAB, hdeD, dps, adiY). Finally, we found that in addition to H-NS and RcsB, a third regulator, HdfR, inversely controls glutamate-dependent acid resistance pathway and motility.

Conclusions: H-NS lies near the top of the hierarchy orchestrating acid response centred on RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways.

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Related in: MedlinePlus

Model of the H-NS-dependent regulatory network in flagella and acid stress control. At the top, H-NS positively controls motility and represses acid stress resistance. Genes in cross symbol are directly activated by H-NS; in rectangle: directly repressed by H-NS; in circle: indirectly repressed by H-NS. Regulatory proteins are indicated with upper case. Orange filling: flagellum synthesis process; Pink filling: glutamate-dependent acid resistance process; Blue filling: arginine-dependent acid resistance process; Red filling: lysine-dependent acid resistance process; Green filling: genes involved in three different acid resistance processes. Gene names in yellow indicate the direct targets of RcsB-P/GadE complex placed at the centre of this regulatory cascade. A positive effect on transcription is indicated by arrows and a negative regulatory effect is indicated by blunt ended lines. Direct regulation is indicated by solid lines. Indirect regulation is indicated by dashed lines. Previously published results are included in the scheme: [1-3,5-7,10,16,32-40].
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Figure 3: Model of the H-NS-dependent regulatory network in flagella and acid stress control. At the top, H-NS positively controls motility and represses acid stress resistance. Genes in cross symbol are directly activated by H-NS; in rectangle: directly repressed by H-NS; in circle: indirectly repressed by H-NS. Regulatory proteins are indicated with upper case. Orange filling: flagellum synthesis process; Pink filling: glutamate-dependent acid resistance process; Blue filling: arginine-dependent acid resistance process; Red filling: lysine-dependent acid resistance process; Green filling: genes involved in three different acid resistance processes. Gene names in yellow indicate the direct targets of RcsB-P/GadE complex placed at the centre of this regulatory cascade. A positive effect on transcription is indicated by arrows and a negative regulatory effect is indicated by blunt ended lines. Direct regulation is indicated by solid lines. Indirect regulation is indicated by dashed lines. Previously published results are included in the scheme: [1-3,5-7,10,16,32-40].

Mentions: H-NS regulates directly and indirectly the RcsB-P/GadE complex, that is located at the centre of the acid resistance network as well as control of motility (Figure 3). Furthermore, H-NS modulates the level of several regulatory proteins, unrelated to this complex (e.g. CadC, AdiY, HdfR) (Table 4 and Figure 2) [3]. Among them, only HdfR was previously known as a H-NS target [3]. The present study revealed that, in addition to its role in motility control, HdfR regulates the glutamate-dependent acid resistance pathway, directly inducing gltBD and indirectly controlling aslB (Table 4 and Figure 1, 3). All the results presented in this work were integrated together with previously published data, to propose a model of the complex H-NS-dependent regulatory network governing motility and acid stress resistance processes in E. coli (Figure 3). The new characterized H-NS targets, CadC and AdiY, have no effect on motility (data not shown) and are involved in the H-NS-dependent regulation of lysine and arginine-dependent response to acid stress, respectively (Table 3). Furthermore, we found that AdiY is also involved in glutamate-dependent response to acid stress (Table 2). It directly or indirectly regulates several genes specific to this response including aslB, gltBD, gadA, gadBC, slp-dctR or having more global role in acid stress resistance such as hdeAB and hdeD (Table 4). Interestingly, we demonstrated that H-NS has a direct control effect on the cadBA promoter (Figure 2), in accordance with the previous suggestion of a competition between the CadC activator and H-NS for binding to this promoter region [23]. In addition to its role in the repression of major regulators at high levels of the hierarchy, we have shown that H-NS is able to directly affect acid stress circuits repressing the transcription of several structural genes (e.g. yhiM, slp, dctR) (Figure 2). This is in agreement with the proposed competition between activation by specific regulators and repression by H-NS, in several bacterial systems [24,25]. The results of present study point out the essential role for several intermediary players within H-NS-dependent regulatory network and suggest an accessory role for other regulators in acid stress response. Indeed, the EvgA-YdeO regulatory pathway plays a secondary modulator role in the glutamate-dependent acid stress response, in comparison to H-NS. In the same means, AslB and YdeP, two anaerobic enzymes, may have a redundant function in this stress response.


Decrypting the H-NS-dependent regulatory cascade of acid stress resistance in Escherichia coli.

Krin E, Danchin A, Soutourina O - BMC Microbiol. (2010)

Model of the H-NS-dependent regulatory network in flagella and acid stress control. At the top, H-NS positively controls motility and represses acid stress resistance. Genes in cross symbol are directly activated by H-NS; in rectangle: directly repressed by H-NS; in circle: indirectly repressed by H-NS. Regulatory proteins are indicated with upper case. Orange filling: flagellum synthesis process; Pink filling: glutamate-dependent acid resistance process; Blue filling: arginine-dependent acid resistance process; Red filling: lysine-dependent acid resistance process; Green filling: genes involved in three different acid resistance processes. Gene names in yellow indicate the direct targets of RcsB-P/GadE complex placed at the centre of this regulatory cascade. A positive effect on transcription is indicated by arrows and a negative regulatory effect is indicated by blunt ended lines. Direct regulation is indicated by solid lines. Indirect regulation is indicated by dashed lines. Previously published results are included in the scheme: [1-3,5-7,10,16,32-40].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2984483&req=5

Figure 3: Model of the H-NS-dependent regulatory network in flagella and acid stress control. At the top, H-NS positively controls motility and represses acid stress resistance. Genes in cross symbol are directly activated by H-NS; in rectangle: directly repressed by H-NS; in circle: indirectly repressed by H-NS. Regulatory proteins are indicated with upper case. Orange filling: flagellum synthesis process; Pink filling: glutamate-dependent acid resistance process; Blue filling: arginine-dependent acid resistance process; Red filling: lysine-dependent acid resistance process; Green filling: genes involved in three different acid resistance processes. Gene names in yellow indicate the direct targets of RcsB-P/GadE complex placed at the centre of this regulatory cascade. A positive effect on transcription is indicated by arrows and a negative regulatory effect is indicated by blunt ended lines. Direct regulation is indicated by solid lines. Indirect regulation is indicated by dashed lines. Previously published results are included in the scheme: [1-3,5-7,10,16,32-40].
Mentions: H-NS regulates directly and indirectly the RcsB-P/GadE complex, that is located at the centre of the acid resistance network as well as control of motility (Figure 3). Furthermore, H-NS modulates the level of several regulatory proteins, unrelated to this complex (e.g. CadC, AdiY, HdfR) (Table 4 and Figure 2) [3]. Among them, only HdfR was previously known as a H-NS target [3]. The present study revealed that, in addition to its role in motility control, HdfR regulates the glutamate-dependent acid resistance pathway, directly inducing gltBD and indirectly controlling aslB (Table 4 and Figure 1, 3). All the results presented in this work were integrated together with previously published data, to propose a model of the complex H-NS-dependent regulatory network governing motility and acid stress resistance processes in E. coli (Figure 3). The new characterized H-NS targets, CadC and AdiY, have no effect on motility (data not shown) and are involved in the H-NS-dependent regulation of lysine and arginine-dependent response to acid stress, respectively (Table 3). Furthermore, we found that AdiY is also involved in glutamate-dependent response to acid stress (Table 2). It directly or indirectly regulates several genes specific to this response including aslB, gltBD, gadA, gadBC, slp-dctR or having more global role in acid stress resistance such as hdeAB and hdeD (Table 4). Interestingly, we demonstrated that H-NS has a direct control effect on the cadBA promoter (Figure 2), in accordance with the previous suggestion of a competition between the CadC activator and H-NS for binding to this promoter region [23]. In addition to its role in the repression of major regulators at high levels of the hierarchy, we have shown that H-NS is able to directly affect acid stress circuits repressing the transcription of several structural genes (e.g. yhiM, slp, dctR) (Figure 2). This is in agreement with the proposed competition between activation by specific regulators and repression by H-NS, in several bacterial systems [24,25]. The results of present study point out the essential role for several intermediary players within H-NS-dependent regulatory network and suggest an accessory role for other regulators in acid stress response. Indeed, the EvgA-YdeO regulatory pathway plays a secondary modulator role in the glutamate-dependent acid stress response, in comparison to H-NS. In the same means, AslB and YdeP, two anaerobic enzymes, may have a redundant function in this stress response.

Bottom Line: RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways plays a central role in the regulatory cascade.Finally, we found that in addition to H-NS and RcsB, a third regulator, HdfR, inversely controls glutamate-dependent acid resistance pathway and motility.H-NS lies near the top of the hierarchy orchestrating acid response centred on RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways.

View Article: PubMed Central - HTML - PubMed

Affiliation: Unité de Plasticité du Génome Bactérien, Institut Pasteur, France. ekrin@pasteur.fr

ABSTRACT

Background: H-NS regulates the acid stress resistance. The present study aimed to characterize the H-NS-dependent cascade governing the acid stress resistance pathways and to define the interplay between the different regulators.

Results: We combined mutational, phenotypic and gene expression analyses, to unravel the regulatory hierarchy in acid resistance involving H-NS, RcsB-P/GadE complex, HdfR, CadC, AdiY regulators, and DNA-binding assays to separate direct effects from indirect ones. RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways plays a central role in the regulatory cascade. However, H-NS also directly controls specific regulators of these pathways (e.g. cadC) and genes involved in general stress resistance (hdeAB, hdeD, dps, adiY). Finally, we found that in addition to H-NS and RcsB, a third regulator, HdfR, inversely controls glutamate-dependent acid resistance pathway and motility.

Conclusions: H-NS lies near the top of the hierarchy orchestrating acid response centred on RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways.

Show MeSH
Related in: MedlinePlus