CRP-cAMP mediates silencing of Salmonella virulence at the post-transcriptional level

Mouali, Youssef El; Gaviria-Cantin, Tania; Sánchez-Romero, María Antonia; Gibert, M. Alsina; Westermann, Alexander J.; Vogel, Jörg; Balsalobre, Carlos

doi:10.1371/journal.pgen.1007401

Cited by 42 publications

(47 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of SirA on Spot 42 expression was assessed, using a chromosomal spf - lacZ in the presence and absence of SirA in both WT and Δ crp genetic backgrounds at logarithmic growth phase. As previously shown, Spot 42 expression is induced in the Δ crp mutant compared to WT ( El Mouali et al, 2018 ; Figure 5A ). Remarkably, no regulation was observed in the absence of SirA and induction of Spot 42 expression in the Δ crp mutant strain is still observed in absence of SirA ( Figure 5A ).…”

Section: Resultssupporting

confidence: 77%

“…In Salmonella , CRP-cAMP represses the expression of the regulatory sRNA Spot 42 in a growth-dependent manner ( El Mouali et al, 2018 ). The similarity of the expression profiles of Spot 42 and CsrC, let us to hypothesize that CRP-cAMP might regulate CsrC via modulation of Spot 42 levels.…”

Section: Resultsmentioning

confidence: 99%

“…Expression studies using S. enterica cultures on solid media indicates that CRP-cAMP, in contrast to its role described in E. coli , positively regulate the expression of CsrB and CsrC via upregulation of sirA ( Teplitski et al, 2006 ). In S. enterica other sRNAs, such as CyaR and Spot 42, are also regulated by CRP-cAMP, acting as an activator for CyaR and as a repressor for Spot 42 ( Papenfort et al, 2008 ; El Mouali et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differential Regulation of CsrC and CsrB by CRP-cAMP in Salmonella enterica

et al. 2020

Self Cite

View full text Add to dashboard Cite

Post-transcriptional regulation mediated by regulatory small RNAs (sRNAs) has risen as a key player in fine-tuning gene expression in response to environmental stimuli. Here, we show that, in Salmonella enterica , the central metabolic regulator CRP-cAMP differentially regulates the sRNAs CsrB and CsrC in a growth phase-dependent manner. While CsrB expression remains unchanged during growth, CsrC displays a growth phase-dependent expression profile, being weakly expressed at the logarithmic growth phase and induced upon entry into stationary phase. We show that CRP-cAMP contributes to the expression pattern of CsrC by repressing its expression during the logarithmic growth phase. The CRP-cAMP mediated repression of CsrC is independent of SirA, a known transcriptional CsrB/CsrC activator. We further show that the sRNA Spot 42, which is derepressed in a Δ crp strain, upregulates CsrC during logarithmic growth. We propose a model where the growth-dependent regulation of CsrC is sustained by the CRP-cAMP-mediated repression of Spot 42. Together, our data point toward a differential regulation of the sRNAs CsrB and CsrC in response to environmental stimuli, leading to fine-tuning of gene expression via the sequestration of the RNA-binding protein CsrA.

show abstract

Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Regulation of CsrC and CsrB by CRP-cAMP in Salmonella enterica

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…The hilD mRNA also has an unusually long ~300 nt 3′ UTR, which apparently affects the stability of the message. Several mechanisms of regulation at the 3′ UTR have been characterized (Lopez‐Garrido et al , ; Gaviria‐Cantin et al , ; El Mouali et al , ).…”

Section: Discussionmentioning

confidence: 99%

Oxygen‐dependent regulation of SPI1 type three secretion system by small RNAs in Salmonella enterica serovar Typhimurium

Kim

Golubeva

Vanderpool

et al. 2018

Molecular Microbiology

View full text Add to dashboard Cite

Summary Salmonella Typhimurium induces inflammatory diarrhea and uptake into intestinal epithelial cells using the Salmonella pathogenicity island 1 (SPI1) type III secretion system (T3SS). Three AraC‐like regulators, HilD, HilC and RtsA, form a feed‐forward regulatory loop that activates transcription of hilA, encoding the activator of the T3SS structural genes. Many environmental signals and regulatory systems are integrated into this circuit to precisely regulate SPI1 expression. A subset of these regulatory factors affects translation of hilD, but the mechanisms are poorly understood. Here, we identified two sRNAs, FnrS and ArcZ, which repress hilD translation, leading to decreased production of HilA. FnrS and ArcZ are oppositely regulated in response to oxygen, one of the key environmental signals affecting expression of SPI1. Mutational analysis demonstrates that FnrS and ArcZ bind to the hilD mRNA 5′ UTR, resulting in translational repression. Deletion of fnrS led to increased HilD production under low‐aeration conditions, whereas deletion of arcZ abolished the regulatory effect on hilD translation aerobically. The fnrS arcZ double mutant has phenotypes in a mouse oral infection model consistent with increased expression of SPI1. Together, these results suggest that coordinated regulation by these two sRNAs maximizes HilD production at an intermediate level of oxygen.

show abstract

“…1). Several regulatory systems have been implicated in controlling hilD mRNA stability or translation, acting at either the 5= untranslated region (UTR) or 3= UTR of the hilD mRNA (20)(21)(22)(23)(24)(25). Other systems directly control hilA expression or more globally affect the entire system (12,(26)(27)(28).…”

mentioning

confidence: 99%

The Small RNA PinT Contributes to PhoP-Mediated Regulation of the Salmonella Pathogenicity Island 1 Type III Secretion System in Salmonella enterica Serovar Typhimurium

et al. 2019

View full text Add to dashboard Cite

Salmonella enterica serovar Typhimurium induces inflammatory diarrhea and bacterial uptake into intestinal epithelial cells using the Salmonella pathogenicity island 1 (SPI1) type III secretion system (T3SS). HilA activates transcription of the SPI1 structural components and effector proteins. Expression of hilA is activated by HilD, HilC, and RtsA, which act in a complex feed-forward regulatory loop. Many environmental signals and other regulators are integrated into this regulatory loop, primarily via HilD. After the invasion of Salmonella into host intestinal epithelial cells or during systemic replication in macrophages, the SPI T3SS is no longer required or expressed. We have shown that the two-component regulatory system PhoPQ, required for intracellular survival, represses the SPI1 T3SS mostly by controlling the transcription of hilA and hilD. Here we show that PinT, one of the PhoPQ-regulated small RNAs (sRNAs), contributes to this regulation by repressing hilA and rtsA translation. PinT base pairs with both the hilA and rtsA mRNAs, resulting in translational inhibition of hilA, but also induces degradation of the rts transcript. PinT also indirectly represses expression of FliZ, a posttranslational regulator of HilD, and directly represses translation of ssrB, encoding the primary regulator of the SPI2 T3SS. Our in vivo mouse competition assays support the concept that PinT controls a series of virulence genes at the posttranscriptional level in order to adapt Salmonella from the invasion stage to intracellular survival. IMPORTANCE Salmonella is one of the most important food-borne pathogens, infecting over one million people in the United States every year. These bacteria use a needle-like device to interact with intestinal epithelial cells, leading to invasion of the cells and induction of inflammatory diarrhea. A complex regulatory network controls expression of the invasion system in response to numerous environmental signals. Here we explore the molecular mechanisms by which the small RNA PinT contributes to this regulation, facilitating inactivation of the system after invasion. PinT controls several important virulence systems in Salmonella, tuning the transition between different stages of infection.

show abstract

CRP-cAMP mediates silencing of Salmonella virulence at the post-transcriptional level

Cited by 42 publications

References 68 publications

Differential Regulation of CsrC and CsrB by CRP-cAMP in Salmonella enterica

Differential Regulation of CsrC and CsrB by CRP-cAMP in Salmonella enterica

Oxygen‐dependent regulation of SPI1 type three secretion system by small RNAs in Salmonella enterica serovar Typhimurium

The Small RNA PinT Contributes to PhoP-Mediated Regulation of the Salmonella Pathogenicity Island 1 Type III Secretion System in Salmonella enterica Serovar Typhimurium

Contact Info

Product

Resources

About