MarA, SoxS and Rob of Escherichia coli – Global Regulators of Multidrug Resistance, Virulence and Stress Response

Duval,

doi:10.6000/1927-3037.2013.02.03.2

Cited by 91 publications

(122 citation statements)

References 218 publications

(326 reference statements)

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“…Expression of the AraC/ XylS family member SoxS has been described to be activated in response to oxidative stress in E. coli and other enterobacteria (15). In the present study, we demonstrated that SoxS from E. amylovora Ea1189 is also involved in superoxide resistance.…”

Section: Figsupporting

confidence: 54%

“…Many genes are under either local or global transcriptional control. For example, the multidrug transporter AcrAB is locally controlled by the transcriptional repressor AcrR in Escherichia coli (10,11) and Salmonella enterica (12) and by global transcriptional activators of the AraC/XylS family, such as MarA, SoxS, and Rob (13)(14)(15).…”

mentioning

confidence: 99%

“…Most members of this family are involved in the control of carbon metabolism, pathogenicity, or stress responses (15,17). In E. coli, the homologous regulators MarA, SoxS, and Rob control about 40 genes involved in resistance to antibiotics, heavy metals, organic solvents, and oxidative stress (19)(20)(21)(22), and together they form the so-called mar/sox/rob regulon, whose function is associated with binding to the so-called marbox, a 20-bp asymmetric sequence (23).…”

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confidence: 99%

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AraC/XylS Family Stress Response Regulators Rob, SoxS, PliA, and OpiA in the Fire Blight Pathogen Erwinia amylovora

2014

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bTranscriptional regulators of the AraC/XylS family have been associated with multidrug resistance, organic solvent tolerance, oxidative stress, and virulence in clinically relevant enterobacteria. In the present study, we identified four homologous AraC/ XylS regulators, Rob, SoxS, PliA, and OpiA, from the fire blight pathogen Erwinia amylovora Ea1189. Previous studies have shown that the regulators MarA, Rob, and SoxS from Escherichia coli mediate multiple-antibiotic resistance, primarily by upregulating the AcrAB-TolC efflux system. However, none of the four AraC/XylS regulators from E. amylovora was able to induce a multidrug resistance phenotype in the plant pathogen. Overexpression of rob led to a 2-fold increased expression of the acrA gene. However, the rob-overexpressing strain showed increased resistance to only a limited number of antibiotics. Furthermore, Rob was able to induce tolerance to organic solvents in E. amylovora by mechanisms other than efflux. We demonstrated that SoxS from E. amylovora is involved in superoxide resistance. A soxS-deficient mutant of Ea1189 was not able to grow on agar plates supplemented with the superoxide-generating agent paraquat. Furthermore, expression of soxS was induced by redox cycling agents. We identified two novel members of the AraC/XylS family in E. amylovora. PliA was highly upregulated during the early infection phase in apple rootstock and immature pear fruits. Multiple compounds were able to induce the expression of pliA, including apple leaf extracts, phenolic compounds, redox cycling agents, heavy metals, and decanoate. OpiA was shown to play a role in the regulation of osmotic and alkaline pH stress responses.

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Section: Figsupporting

confidence: 54%

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confidence: 99%

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confidence: 99%

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AraC/XylS Family Stress Response Regulators Rob, SoxS, PliA, and OpiA in the Fire Blight Pathogen Erwinia amylovora

2014

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“…The nature of the role played by MgrA toward tetR21 expression was not clear, since a lack of MgrA did not lead to an obvious change in the level of tetR21 expression in either direction. Many multidrug efflux pumps in Gram-negative bacteria like E. coli, K. pneumoniae, and E. cloacae are controlled by special regulatory systems that mediate responses to hostile environments (37). In addition, studies of Gram-negative efflux pumps revealed that the expression of several transporters of the RND (resistance-nodulation-division) family of multidrug (MDR) transporters were induced by and transported cellular metabolites as part of the bacterial cell physiology (38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Role of the Tet38 Efflux Pump in Staphylococcus aureus Internalization and Survival in Epithelial Cells

et al. 2015

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bWe previously identified the protein Tet38 as a chromosomally encoded efflux pump of Staphylococcus aureus that confers resistance to tetracycline and certain unsaturated fatty acids. Tet38 also contributes to mouse skin colonization. In this study, we discovered a novel regulator of tet38, named tetracycline regulator 21 (TetR21), that bound specifically to the tet38 promoter and repressed pump expression. A ⌬tetR21 mutant showed a 5-fold increase in tet38 transcripts and an 8-fold increase in resistance to tetracycline and fatty acids. The global regulator MgrA bound to the tetR21 promoter and indirectly repressed the expression of tet38. To further assess the full role of Tet38 in S. aureus adaptability, we tested its effect on host cell invasion using A549 (lung) and HMEC-1 (heart) cell lines. We used S. aureus RN6390, its ⌬tet38, ⌬tetR21, and ⌬mgrA mutants, and a ⌬tet38 ⌬tetR21 double mutant. After 2 h of contact, the ⌬tet38 mutant was internalized in 6-fold-lower numbers than RN6390 in A549 and HMEC-1 cells, and the ⌬tetR21 mutant was internalized in 2-fold-higher numbers than RN6390. A slight increase of 1.5-fold in internalization was found for the ⌬mgrA mutant. The growth patterns of RN6390 and the ⌬mgrA and ⌬tetR21 mutants within A549 cells were similar, while no growth was observed for the ⌬tet38 mutant. These data indicate that the Tet38 efflux pump is regulated by TetR21 and contributes to the ability of S. aureus to internalize and replicate within epithelial cells.

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“…T ranscription factors of pathogenic bacteria can be important virulence determinants, since they control genes that specify toxins, proteins functioning in nutrient acquisition within the hostile host environment, and products that operate by subverting the host innate immunity (1)(2)(3)(4). For example, in Bacillus anthracis, the causative agent of the zoonotic infectious disease, anthrax, the plasmid-borne atxA gene encodes a transcription factor required for virulence, since it is necessary for the activation of genes for toxin and protective capsule production (5,6).…”

mentioning

confidence: 99%

Evidence that Oxidative Stress Induces spxA2 Transcription in Bacillus anthracis Sterne through a Mechanism Requiring SpxA1 and Positive Autoregulation

et al. 2016

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Bacillus anthracis possesses two paralogs of the transcriptional regulator, Spx. SpxA1 and SpxA2 interact with RNA polymerase (RNAP) to activate the transcription of genes implicated in the prevention and alleviation of oxidative protein damage. The spxA2 gene is highly upregulated in infected macrophages, but how this is achieved is unknown. Previous studies have shown that the spxA2 gene was under negative control by the Rrf2 family repressor protein, SaiR, whose activity is sensitive to oxidative stress. These studies also suggested that spxA2 was under positive autoregulation. In the present study, we show by in vivo and in vitro analyses that spxA2 is under direct autoregulation but is also dependent on the SpxA1 paralogous protein. The deletion of either spxA1 or spxA2 reduced the diamide-inducible expression of an spxA2-lacZ construct. In vitro transcription reactions using purified B. anthracis RNAP showed that SpxA1 and SpxA2 protein stimulates transcription from a DNA fragment containing the spxA2 promoter. Ectopically positioned spxA2-lacZ fusion requires both SpxA1 and SpxA2 for expression, but the requirement for SpxA1 is partially overcome when saiR is deleted. Electrophoretic mobility shift assays showed that SpxA1 and SpxA2 enhance the affinity of RNAP for spxA2 promoter DNA and that this activity is sensitive to reductant. We hypothesize that the previously observed upregulation of spxA2 in the oxidative environment of the macrophage is at least partly due to SpxA1-mediated SaiR repressor inactivation and the positive autoregulation of spxA2 transcription. T ranscription factors of pathogenic bacteria can be important virulence determinants, since they control genes that specify toxins, proteins functioning in nutrient acquisition within the hostile host environment, and products that operate by subverting the host innate immunity (1-4). For example, in Bacillus anthracis, the causative agent of the zoonotic infectious disease, anthrax, the plasmid-borne atxA gene encodes a transcription factor required for virulence, since it is necessary for the activation of genes for toxin and protective capsule production (5, 6). Other Grampositive bacteria possess genes encoding one or more forms of the ArsC (arsenate reductase) family protein, Spx, which is an RNA polymerase (RNAP)-binding protein directing the expression of large regulons that include genes necessary for pathogenesis (7-11). Studies of streptococci, Listeria monocytogenes, Staphylococcus aureus, and Enterococcus spp. have demonstrated the requirement for Spx proteins for virulence and viability (7,8,(12)(13)(14)(15). IMPORTANCE Regulators of transcription initiationSpx was detected in studies of B. subtilis, in which it is encoded by a gene that is under complex transcriptional control involving four RNAP forms and two repressors (16)(17)(18)(19). The complex control of spx transcription operates in response to various stress conditions, such as oxidative and cell envelope stress. Spx protein levels increase under conditions caus...

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MarA, SoxS and Rob of Escherichia coli – Global Regulators of Multidrug Resistance, Virulence and Stress Response

Cited by 91 publications

References 218 publications

AraC/XylS Family Stress Response Regulators Rob, SoxS, PliA, and OpiA in the Fire Blight Pathogen Erwinia amylovora

AraC/XylS Family Stress Response Regulators Rob, SoxS, PliA, and OpiA in the Fire Blight Pathogen Erwinia amylovora

Role of the Tet38 Efflux Pump in Staphylococcus aureus Internalization and Survival in Epithelial Cells

Evidence that Oxidative Stress Induces spxA2 Transcription in Bacillus anthracis Sterne through a Mechanism Requiring SpxA1 and Positive Autoregulation

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