scholarly journals SoxS represses flagellar gene expression through RflP in Salmonella enterica Serovar Typhimurium

2020 ◽  
Author(s):  
Srinivas S. Thota ◽  
Brittany N. Henry ◽  
Lon M. Chubiz
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Transcription Factors ◽  
Salmonella Enterica ◽  
Response Regulator ◽  
Flagellar Gene ◽  
Treatment And Prevention ◽  
Intracellular Signals ◽  
Serovar Typhimurium ◽  
Close Relatives

ABSTRACTFlagellar gene expression is subject to regulation by many global transcription factors in response to environmental and nutritional signals. One of the primary ways this occurs in Salmonella enterica serovar Typhimurium, and its close relatives, is through controlling levels of FlhD4C2 (the flagellar master regulator) via transcriptional, post-transcriptional, and post-translational mechanisms. Recently, we found the homologous transcription factors MarA, Rob, and SoxS repress flhDC expression by distinct mechanisms. MarA and Rob, regulators involved in inducible multidrug resistance, repressed flhDC transcription by interacting directly with the flhDC promoter. Alternatively, SoxS, the oxidative stress response regulator, altered FlhD4C2 levels independent of flhDC transcription by post-transcriptional or post-translational mechanism. Here, using a forward genetic screen, we discovered that SoxS-dependent repression of flagellar gene expression occurs through RflP, an anti-FlhD4C2 factor that targets FlhD4C2 for proteolytic degradation. Elevated soxS expression resulted in concomitant increases in rflP expression, indicating SoxS may work through RflP at the level of rflP transcription. Mapping of the rflP promoter and a bioinformatic search yielded a putative SoxS binding site proximal to the rflP transcription start site. Comparison of the rflP promoter region in S. Typhimurium and Escherichia coli indicate substantial differences, providing a possible mechanism for differential expression of rflP between these species.IMPORTANCESalmonella enterica is a major cause of foodborne illness. Understanding environmental and intracellular signals used by Salmonella to control expression of virulence-associated traits is critical to advancing treatment and prevention of Salmonella-related disease. Reduced expression of flagella at key points during Salmonella infection aids in evasion of the host innate immune system. Within macrophages Salmonella is non-flagellated and exposed to oxidative stress. SoxS-dependent repression of flagellar genes may provide a potential link between oxidative stress and reductions in flagellar expression.

scholarly journals Multiple Factors Independently RegulatehilA and Invasion Gene Expression in Salmonella enterica Serovar Typhimurium

2000 ◽  
Vol 182 (7) ◽  
pp. 1872-1882 ◽  
Author(s):  
Robin L. Lucas ◽  
C. Phoebe Lostroh ◽  
Concetta C. DiRusso ◽  
Michael P. Spector ◽  
Barry L. Wanner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Salmonella Enterica ◽  
Inorganic Phosphate ◽  
Response Regulator ◽  
Regulatory System ◽  
Negative Control ◽  
Host Cells ◽  
Uptake System ◽  
Intracellular Signals ◽  
Serovar Typhimurium

HilA activates the expression of Salmonella entericaserovar Typhimurium invasion genes. To learn more about regulation ofhilA, we isolated Tn5 mutants exhibiting reduced hilA and/or invasion gene expression. In addition to expected mutations, we identified Tn5 insertions inpstS, fadD, flhD, flhC, and fliA. Analysis of the pstS mutant indicates that hilA and invasion genes are repressed by the response regulator PhoB in the absence of the Pst high-affinity inorganic phosphate uptake system. This system is required for negative control of the PhoR-PhoB two-component regulatory system, suggesting thathilA expression may be repressed by PhoR-PhoB under low extracellular inorganic phosphate conditions. FadD is required for uptake and degradation of long-chain fatty acids, and our analysis of the fadD mutant indicates that hilA is regulated by a FadD-dependent, FadR-independent mechanism. Thus, fatty acid derivatives may act as intracellular signals to regulatehilA expression. flhDC and fliAencode transcription factors required for flagellum production, motility, and chemotaxis. Complementation studies with flhCand fliA mutants indicate that FliZ, which is encoded in an operon with fliA, activates expression of hilA, linking regulation of hilA with motility. Finally, epistasis tests showed that PhoB, FadD, FliZ, SirA, and EnvZ act independently to regulate hilA expression and invasion. In summary, our screen has identified several distinct pathways that can modulate S. enterica serovar Typhimurium's ability to express hilA and invade host cells. Integration of signals from these different pathways may help restrict invasion gene expression during infection.

scholarly journals Multidrug Resistance Regulators MarA, SoxS, Rob, and RamA Repress Flagellar Gene Expression and Motility in Salmonella enterica Serovar Typhimurium

2019 ◽  
Vol 201 (23) ◽  
Author(s):  
Srinivas S. Thota ◽  
Lon M. Chubiz
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Multidrug Resistance ◽  
Related Species ◽  
Salmonella Enterica ◽  
Mrna Translation ◽  
Flagellar Gene ◽  
Content Type ◽  
E Coli ◽  
Serovar Typhimurium

ABSTRACT Production of flagella is costly and subject to global multilayered regulation, which is reflected in the hierarchical control of flagellar production in many bacterial species. For Salmonella enterica serovar Typhimurium and its relatives, global regulation of flagellar production primarily occurs through the control of flhDC transcription and mRNA translation. In this study, the roles of the homologous multidrug resistance regulators MarA, SoxS, Rob, and RamA (constituting the mar-sox-rob regulon in S. Typhimurium) in regulating flagellar gene expression were explored. Each of these regulators was found to inhibit flagellar gene expression, production of flagella, and motility. To different degrees, repression via these transcription factors occurred through direct interactions with the flhDC promoter, particularly for MarA and Rob. Additionally, SoxS repressed flagellar gene expression via a posttranscriptional pathway, reducing flhDC translation. The roles of these transcription factors in reducing motility in the presence of salicylic acid were also elucidated, adding a genetic regulatory element to the response of S. Typhimurium to this well-characterized chemorepellent. Integration of flagellar gene expression into the mar-sox-rob regulon in S. Typhimurium contrasts with findings for closely related species such as Escherichia coli, providing an example of plasticity in the mar-sox-rob regulon throughout the Enterobacteriaceae family. IMPORTANCE The mar-sox-rob regulon is a large and highly conserved stress response network in the Enterobacteriaceae family. Although it is well characterized in E. coli, the extent of this regulon in related species is unclear. Here, the control of costly flagellar gene expression is connected to the mar-sox-rob regulon of S. Typhimurium, contrasting with the E. coli regulon model. These findings demonstrate the flexibility of the mar-sox-rob regulon to accommodate novel regulatory targets, and they provide evidence for its broader regulatory role within this family of diverse bacteria.

scholarly journals Pathways Leading from BarA/SirA to Motility andVirulence Gene Expression inSalmonella

2003 ◽  
Vol 185 (24) ◽  
pp. 7257-7265 ◽  
Author(s):  
Max Teplitski ◽  
Robert I. Goodier ◽  
Brian M. M. Ahmer
Keyword(s):  
Gene Expression ◽  
Response Regulator ◽  
Flagellar Gene ◽  
Virulence Determinants ◽  
Mobility Shift ◽  
Serovar Typhimurium ◽  
Regulatory Cascades ◽  
Flagellar Regulon ◽  
Membrane Spanning ◽  
Gel Mobility Shift

ABSTRACT The barA and sirA genes of Salmonella enterica serovar Typhimurium encode a two-component sensor kinase and a response regulator, respectively. This system increases the expression of virulence genes and decreases the expression of motility genes. In this study, we examined the pathways by which SirA affects these genes. We found that the master regulator of flagellar genes, flhDC, had a positive regulatory effect on the primary regulator of intestinal virulence determinants, hilA, but that hilA had no effect on flhDC. SirA was able to repress flhDC in a hilA mutant and activate hilA in an flhDC mutant. Therefore, although the flhDC and hilA regulatory cascades interact, sirA affects each of them independently. A form of BarA lacking the two N-terminal membrane-spanning domains, BarA198, autophosphorylates in the presence of ATP and transfers the phosphate to purified SirA. Phosphorylated SirA was found to directly bind the hilA and hilC promoters in gel mobility shift assays but not the flhD, fliA, hilD, and invF promoters. Given that the CsrA/csrB system is known to directly affect flagellar gene expression, we tested the hypothesis that SirA affects flagellar gene expression indirectly by regulating csrA or csrB. The sirA gene did not regulate csrA but did activate csrB expression. Consistent with these results, phosphorylated SirA was found to directly bind the csrB promoter but not the csrA promoter. We propose a model in which SirA directly activates virulence expression via hilA and hilC while repressing the flagellar regulon indirectly via csrB.

scholarly journals Sub-Inhibitory Fosmidomycin Exposures Elicits Oxidative Stress in Salmonella enterica Serovar typhimurium LT2

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e95271 ◽  
Author(s):  
David T. Fox ◽  
Emily N. Schmidt ◽  
Hongzhao Tian ◽  
Suraj Dhungana ◽  
Michael C. Valentine ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Serovar Typhimurium

Activation of hilA expression at low pH requires the signal sensor CpxA, but not the cognate response regulator CpxR, in Salmonella enterica serovar Typhimurium

Microbiology ◽  
2003 ◽  
Vol 149 (10) ◽  
pp. 2809-2817 ◽  
Author(s):  
Shu-ichi Nakayama ◽  
Akira Kushiro ◽  
Takashi Asahara ◽  
Ryu-ichiro Tanaka ◽  
Lan Hu ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Cell Invasion ◽  
Salmonella Enterica ◽  
Response Regulator ◽  
Low Ph ◽  
Apparent Difference ◽  
Virulence Determinants ◽  
Serovar Typhimurium ◽  
Cognate Response Regulator ◽  
Invasion Capacity

A two-component regulatory system, cpxR–cpxA, plays an important role in the pH-dependent regulation of virF, a global activator for virulence determinants including invasion genes, in Shigella sonnei. The authors examined whether the cpxR–cpxA homologues have some function in the expression of Salmonella enterica serovar Typhimurium invasion genes via the regulation of hilA, an activator for these genes. In a Salmonella cpxA mutant, the hilA expression level was reduced to less than 10 % of that in the parent strain at pH 6·0. This mutant strain also showed undetectable synthesis of an invasion gene product, SipC, at pH 6·0 and reduced cell invasion capacity – as low as 20 % of that of the parent. In this mutant, the reduction in hilA expression was much less marked at pH 8·0 than at pH 6·0 – no less than 50 % of that in the parent, and no significant reduction was observed in either SipC synthesis or cell invasion rate, compared to the parent. Unexpectedly, a Salmonella cpxR mutant strain and the parent showed no apparent difference in all three characteristics described above at either pH. These results indicate that in Salmonella, the sensor kinase CpxA activates hilA, and consequently, invasion genes and cell invasion capacity at pH 6·0. At pH 8·0, however, CpxA does not seem to have a large role in activation of these factors. Further, the results show that this CpxA-mediated activation does not require its putative cognate response regulator, CpxR. This suggests that CpxA may interact with regulator(s) other than CpxR to achieve activation at low pH.

scholarly journals Regulation of igaA and the Rcs System by the MviA Response Regulator in Salmonella enterica

2009 ◽  
Vol 191 (8) ◽  
pp. 2743-2752 ◽  
Author(s):  
Clara B. García-Calderón ◽  
Josep Casadesús ◽  
Francisco Ramos-Morales
Keyword(s):  
Membrane Protein ◽  
Salmonella Enterica ◽  
Response Regulator ◽  
Regulatory System ◽  
Enteric Bacteria ◽  
Lon Protease ◽  
Dependent Manner ◽  
Independent Manner ◽  
Serovar Typhimurium

ABSTRACT IgaA is a membrane protein that prevents overactivation of the Rcs regulatory system in enteric bacteria. Here we provide evidence that igaA is the first gene in a σ70-dependent operon of Salmonella enterica serovar Typhimurium that also includes yrfG, yrfH, and yrfI. We also show that the Lon protease and the MviA response regulator participate in regulation of the igaA operon. Our results indicate that MviA regulates igaA transcription in an RpoS-dependent manner, but the results also suggest that MviA may regulate RcsB activation in an RpoS- and IgaA-independent manner.

scholarly journals The fimYZ Genes Regulate Salmonella enterica Serovar Typhimurium Invasion in Addition to Type 1 Fimbrial Expression and Bacterial Motility

2005 ◽  
Vol 73 (3) ◽  
pp. 1377-1385 ◽  
Author(s):  
M. Aaron Baxter ◽  
Bradley D. Jones
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Protein Interactions ◽  
Salmonella Enterica ◽  
Negative Regulator ◽  
Invasive Phenotype ◽  
Environmental Signals ◽  
Bacterial Physiology ◽  
Serovar Typhimurium

ABSTRACT An important step in Salmonella enterica serovar Typhimurium virulence is the ability to invade the intestinal epithelium. The invasion process requires a large number of genes encoded on Salmonella pathogenicity island 1 (SPI-1) at centisome 63 as well as genes located in other positions throughout the chromosome. Expression of the invasive phenotype is tightly regulated by environmental cues that are processed by a complex regulatory scheme. A central player in the invasion regulatory pathway is the HilA protein, which is transcriptional activator belonging to the OmpR/ToxR family. A number of positive regulators (hilC, hilD, fis, sirA/barA, csrAB, phoBR, fadD, envZ/ompR, and fliZ) and negative regulators (hha, hilE, lon, ams, phoP c and pag) have been identified that are able to alter expression of hilA transcription. Recent work has found that hilA transcription requires the HilD protein for activation. Other work has emphasized the importance of HilE as a negative regulator of hilA. Overexpression of hilE superrepresses hilA transcription, as well as the invasive phenotype. Two-hybrid experiments suggest that HilE exerts its regulatory influence on hilA through protein-protein interactions with HilD as the protein does not bind to the hilA promoter nor does it affect hilD transcription. As it seems likely that hilE plays an important role in translating environmental signals into invasion gene regulation, we have attempted to identify how the hilE gene itself is regulated. Our results indicate that the fimYZ genes, response regulatory proteins involved in type 1 fimbrial gene expression and recently implicated in motility gene regulation, are important activators of hilE expression. These findings indicate that invasion gene expression is coregulated with motility and adherence and provide experimental evidence that the expression of these virulence phenotypes is a subset of the overall regulation of bacterial physiology.

DsrA confers resistance to oxidative stress in Salmonella enterica serovar Typhimurium

Food Control ◽  
2021 ◽  
Vol 121 ◽  
pp. 107571
Author(s):  
Rui Dong ◽  
Xiaojie Qin ◽  
Shoukui He ◽  
Xiujuan Zhou ◽  
Yan Cui ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Serovar Typhimurium
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