Aromatic Acid Metabolites of
            <i>Escherichia coli</i>
            K-12 Can Induce the
            <i>marRAB</i>
            Operon

Chubiz, Lon M.; Rao, Christopher V.

doi:10.1128/jb.00371-10

Cited by 44 publications

(46 citation statements)

References 23 publications

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“…Like salicylate (56,57), which is the archetypal activator of marRAB, 2,3-dihydroxybenzoic acid was found to bind MarR, whereas anthranilate and pHBA did not. Chubiz and Rao (55) suggested that anthranilate and pHBA activate marRAB transcription through a mechanism that does not involve MarR. Interestingly, we previously observed partial induction of marRAB transcription via a non-MarRAB pathway (i) by salicylate (39,58,59) and (ii) in a tolC mutant (20).…”

Section: Discussionmentioning

confidence: 98%

“…Since pHBA is an intermediate in ubiquinone biosynthesis, the authors suggested that the AaeAB efflux system was a "metabolic relief valve" in the event of high cellular pHBA concentrations. Chubiz and Rao (55) found that marRAB transcription is activated by 2,3-dihydroxybenzoic acid and anthranilate, which are intermediates in enterobactin and tryptophan biosynthesis, respectively, and also by pHBA. Like salicylate (56,57), which is the archetypal activator of marRAB, 2,3-dihydroxybenzoic acid was found to bind MarR, whereas anthranilate and pHBA did not.…”

Section: Discussionmentioning

confidence: 99%

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Reduction of Cellular Stress by TolC-Dependent Efflux Pumps in Escherichia coli Indicated by BaeSR and CpxARP Activation of spy in Efflux Mutants

Rosner

Martin

2012

Journal of Bacteriology

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Escherichia coli has nine inner membrane efflux pumps which complex with the outer membrane protein TolC and cognate membrane fusion proteins to form tripartite transperiplasmic pumps with diverse functions, including the expulsion of antibiotics. We recently observed that tolC mutants have elevated activities for three stress response regulators, MarA, SoxS, and Rob, and we suggested that TolC-dependent efflux is required to prevent the accumulation of stressful cellular metabolites. Here, we used spy::lacZ fusions to show that two systems for sensing/repairing extracytoplasmic stress, BaeRS and CpxARP, are activated in the absence of TolC-dependent efflux. In either tolC mutants or bacteria with mutations in the genes for four TolC-dependent efflux pumps, spy expression was increased 6-to 8-fold. spy encodes a periplasmic chaperone regulated by the BaeRS and CpxARP stress response systems. The overexpression of spy in tolC or multiple efflux pump mutants also depended on these systems. spy overexpression was not due to acetate, ethanol, or indole accumulation, since external acetate had only a minor effect on wild-type cells, ethanol had a large effect that was not CpxA dependent, and a tolC tnaA mutant which cannot accumulate internal indole overexpressed spy. We propose that, unless TolC-dependent pumps excrete certain metabolites, the metabolites accumulate and activate at least five different stress response systems.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Reduction of Cellular Stress by TolC-Dependent Efflux Pumps in Escherichia coli Indicated by BaeSR and CpxARP Activation of spy in Efflux Mutants

Rosner

Martin

2012

Journal of Bacteriology

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“…MarR homologues control pathways that are critical to bacterial physiology such as stress responses (41,42), virulence (43), metabolism (10), and multiple-drug resistance (23,44,45). The activity of a subset of these proteins can be modified through the formation of a disulfide bond (19,41,46).…”

Section: Discussionmentioning

confidence: 99%

Mutational Analysis of the Multiple-Antibiotic Resistance Regulator MarR Reveals a Ligand Binding Pocket at the Interface between the Dimerization and DNA Binding Domains

et al. 2013

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The Escherichia coli regulator MarR represses the multiple-antibiotic resistance operon marRAB and responds to phenolic compounds, including sodium salicylate, which inhibit its activity. Crystals obtained in the presence of a high concentration of salicylate indicated two possible salicylate sites, SAL-A and SAL-B. However, it was unclear whether these sites were physiologically significant or were simply a result of the crystallization conditions. A study carried out on MarR homologue MTH313 suggested the presence of a salicylate binding site buried at the interface between the dimerization and the DNA-binding domains. Interestingly, the authors of the study indicated a similar pocket conserved in the MarR structure. Since no mutagenesis analysis had been performed to test which amino acids were essential in salicylate binding, we examined the role of residues that could potentially interact with salicylate. We demonstrated that mutations in residues shown as interacting with salicylate at SAL-A and SAL-B in the MarR-salicylate structure had no effect on salicylate binding, indicating that these sites were not the physiological regulatory sites. However, some of these residues (P57, R86, M74, and R77) were important for DNA binding. Furthermore, mutations in residues R16, D26, and K44 significantly reduced binding to both salicylate and 2,4-dinitrophenol, while a mutation in residue H19 impaired the binding to 2,4-dinitrophenol only. These findings indicate, as for MTH313, the presence of a ligand binding pocket located between the dimerization and DNA binding domains.

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“…Taken together, our data demonstrate that TolC affects toxT expression only under certain growth conditions. Recently, a lack of TolC was reported to affect cellular metabolism in E. coli (5), including reports that some metabolites that are exported via TolC modulate gene expression in E. coli (4,20). Thus, we propose that TolC modulates toxT gene expression by modulating TcpP/H activity via accumulation of certain metabolites in V. cholerae.…”

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confidence: 97%

TolC Affects Virulence Gene Expression in Vibrio cholerae

Minato

Siefken

Häse

2011

Journal of Bacteriology

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A Vibrio cholerae tolC mutant showed increased toxT expression in M9 medium, but not in the presence of four amino acids that induce cholera toxin production, and in LB with high osmolarity but not high pH or temperature. TolC did not affect expression of other regulatory genes in the ToxR regulon.TolC is a major outer membrane protein involved in bacterial multidrug resistance and survival of pathogens during infection in several Gram-negative bacteria (12). In Vibrio cholerae, TolC is important for bile resistance, intestinal colonization (1), and RTX toxin secretion (2); however, the role of TolC in virulence gene expression has not been reported.Expression of the main virulence factors, toxin-coregulated pilus (TCP) and cholera toxin (CT), in V. cholerae is tightly regulated in response to various signals, but relatively little is known about the mechanisms of sensing environmental conditions. We screened over 10,000 transposon mutants of the classical biotype of V. cholerae O395N1 (10) and isolated a mutant strain carrying a transposon insertion in the tolC gene that showed increased toxT::lacZ expression compared to that of the parent strain when grown in M9 medium-glycerol (data not shown). Defined tolC mutant strains were generated by homologous recombination essentially as described previously (7). In brief, a two-step PCR of a cat cassette flanked by long (1,000-nucleotide) homologous extensions of the target gene was performed. The resulting PCR product was cloned into pCR2.1 (Invitrogen) using Escherichia coli TOP10 as a host. The resulting plasmid was then restricted by BcuI and NotI, and the desired DNA fragment of approximately 3 kbp was purified from an agarose gel using the QIAquick gel extraction kit (Qiagen), cloned into the BcuI and NotI sites of pWM91 (18), and transformed into the E. coli SM10 pir strain (19). The resulting strain was conjugated with V. cholerae O395N1 or its toxT::lacZ derivative strain (10, 17). The tolC mutations in these strains were verified by PCR.It is known that V. cholerae grown in minimal medium expresses TCP and CT only in the presence of certain amino acids (asparagine, arginine, serine, and glutamate; NRES) (19). The defined V. cholerae O395N1 toxT::lacZ tolC mutant strain revealed higher toxT expression in M9 medium supplemented with different carbon sources but was insensitive to the addition of NRES, regardless of the carbon source (Fig. 1). Consistent with the toxT::lacZ expression data, the defined V. cholerae O395N1 tolC mutant strain showed considerably higher CT production than the wild-type parent strain in M9 medium supplemented with different carbon sources (Table 1), whereas these strains produced comparable amounts of CT when grown in the presence of NRES (Table 1). CT levels were measured essentially as described previously (8). Together, these results showed that a loss of TolC positively affects toxT expression and CT production in V. cholerae O395N1 under specific growth conditions. It was recently suggested that TolC exports cyclic AMP (cAMP) ...

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Aromatic Acid Metabolites of Escherichia coli K-12 Can Induce the marRAB Operon

Cited by 44 publications

References 23 publications

Reduction of Cellular Stress by TolC-Dependent Efflux Pumps in Escherichia coli Indicated by BaeSR and CpxARP Activation of spy in Efflux Mutants

Reduction of Cellular Stress by TolC-Dependent Efflux Pumps in Escherichia coli Indicated by BaeSR and CpxARP Activation of spy in Efflux Mutants

Mutational Analysis of the Multiple-Antibiotic Resistance Regulator MarR Reveals a Ligand Binding Pocket at the Interface between the Dimerization and DNA Binding Domains

TolC Affects Virulence Gene Expression in Vibrio cholerae

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