Antagonistic Role of H-NS and GadX in the Regulation of the Glutamate Decarboxylase-dependent Acid Resistance System in Escherichia coli

Giangrossi, Mara; Zattoni, Stefano; Tramonti, Angela; Biase, Daniela De; Falconi, Maurizio

doi:10.1074/jbc.m413255200

Cited by 52 publications

(66 citation statements)

References 43 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2A and B, the only gene that affected these systems was gadE. The gadA, -X, and W genes, with proven roles in acid resistance, were tested in earlier studies (16,33,44,50,52). Failure to see an effect of the other AFI genes (yhiF, yhiD, hdeB, hdeA, hdeD, or yhiUV) conflicted with some of the earlier studies noted above but suggested that the methodology of testing is important in revealing the roles of these gene products.…”

Section: Resultsmentioning

confidence: 99%

“…Most notable are gadA, encoding an isozyme of glutamate decarboxylase (45,47), and gadE, the essential activator of glutamate-dependent acid resistance (22,30). Two other genes in this region, GadX and GadW, are involved in modulating gadE expression as well as the expression of gadA and gadBC (16,32,33,44,(48)(49)(50)52). However, the contribution of other AFI genes toward acid resistance has remained unclear.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Products of theEscherichia coliAcid Fitness Island Attenuate Metabolite Stress at Extremely Low pH and Mediate a Cell Density-Dependent Acid Resistance

2007

View full text Add to dashboard Cite

Escherichia coli has an ability, rare among the Enterobacteriaceae, to survive extreme acid stress under various host (e.g., human stomach) and nonhost (e.g., apple cider) conditions. Previous microarray studies have exposed a cluster of 12 genes at 79 centisomes collectively called an acid fitness island (AFI). Four AFI genes, gadA, gadX, gadW, and gadE, were already known to be involved in an acid resistance system that consumes an intracellular proton through the decarboxylation of glutamic acid. However, roles for the other eight AFI gene products were either unknown or subject to conflicting findings. Two new aspects of acid resistance are described that require participation of five of the remaining eight AFI genes. YhiF (a putative regulatory protein), lipoprotein Slp, and the periplasmic chaperone HdeA protected E. coli from organic acid metabolites produced during fermentation once the external pH was reduced to pH 2.5. HdeA appears to handle protein damage caused when protonated organic acids diffuse into the cell and dissociate, thereby decreasing internal pH. In contrast, YhiF-and Slp-dependent systems appear to counter the effects of the organic acids themselves, specifically succinate, lactate, and formate, but not acetate. A second phenomenon was defined by two other AFI genes, yhiD and hdeD, encoding putative membrane proteins. These proteins participate in an acid resistance mechanism exhibited only at high cell densities (>10 8 CFU per ml). Densitydependent acid resistance does not require any demonstrable secreted factor and may involve cell contactdependent activation. These findings further define the complex physiology of E. coli acid resistance.

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Products of theEscherichia coliAcid Fitness Island Attenuate Metabolite Stress at Extremely Low pH and Mediate a Cell Density-Dependent Acid Resistance

2007

View full text Add to dashboard Cite

show abstract

“…Regulation of the hdeAB operon. The figure has been produced using data from the literature (8,13,16,20,22,24,26,27,30,33,37,39,42,43,44,46) as well as the results obtained in this study. Thick arrows represent genes.…”

Section: Resultsmentioning

confidence: 99%

Role of the Multidrug Resistance Regulator MarA in Global Regulation of the hdeAB Acid Resistance Operon in Escherichia coli

2008

View full text Add to dashboard Cite

MarA, a transcriptional regulator in Escherichia coli, affects functions such as multiple-antibiotic resistance (Mar) and virulence. Usually an activator, MarA is a repressor of hdeAB and other acid resistance genes. We found that, in wild-type cells grown in LB medium at pH 7.0 or pH 5.5, repression of hdeAB by MarA occurred only in stationary phase and was reduced in the absence of H-NS and GadE, the main regulators of hdeAB. Moreover, repression of hdeAB by MarA was greater in the absence of GadX or Lrp in exponential phase at pH 7.0 and in the absence of GadW or RpoS in stationary phase at pH 5.5. In turn, MarA enhanced repression of hdeAB by H-NS and hindered activation by GadE in stationary phase and also reduced the activity of GadX, GadW, RpoS, and Lrp on hdeAB under some conditions. As a result of its direct and indirect effects, overexpression of MarA prevented most of the induction of hdeAB expression as cells entered stationary phase and made the cells sevenfold more sensitive to acid challenge at pH 2.5. These findings show that repression of hdeAB by MarA depends on pH, growth phase, and other regulators of hdeAB and is associated with reduced resistance to acid conditions.

show abstract

“…The gadA (monocistronic) and gadB (processed) mRNAs are similar lengths (approximately 1.5 kb) and therefore have similar electrophoretic mobilities on an agarose gel. The H-NS binding sites responsible for gadA repression (14) are indicated. The GadX/GadW binding sites described in this paper are indicated by solid ellipses.…”

mentioning

confidence: 99%

Mechanisms of Transcription Activation Exerted by GadX and GadW at the gadA and gadBC Gene Promoters of the Glutamate-Based Acid Resistance System in Escherichia coli

et al. 2006

Self Cite

View full text Add to dashboard Cite

In Escherichia coli the gad system protects the cell from the extreme acid stress encountered during transit through the host stomach. The structural genes gadA, gadB, and gadC encode two glutamate decarboxylase isoforms and a glutamate/␥-aminobutyrate (GABA) antiporter, respectively. Glutamate decarboxylation involves both proton consumption and production of GABA, a neutral compound which is finally exported via the GadC antiporter. Regulation of gadA and gadBC transcription is very complex, involving several circuits controlling expression under different growth phase, medium, and pH conditions. In this study we found that the AraC-like activators GadX and GadW share the same 44-bp binding sites in the gadA and gadBC regulatory regions. The common binding sites are centered at 110.5 bp and 220.5 bp upstream of the transcriptional start points of the gadA and gadBC genes, respectively. At the gadA promoter this regulatory element overlaps one of the binding sites of the repressor H-NS. The DNA of the gadBC promoter has an intrinsic bend which is centered at position ؊121. These findings, combined with transcriptional regulation studies, may account for the two different mechanisms of transcriptional activation by GadX and GadW at the two promoters studied. We speculate that while at the gadA promoter GadX and GadW activate transcription by displacing H-NS via an antirepressor mechanism, at the gadBC promoter the mechanism of activation involves looping of the DNA sequence between the promoter and the activator binding site.

show abstract

Antagonistic Role of H-NS and GadX in the Regulation of the Glutamate Decarboxylase-dependent Acid Resistance System in Escherichia coli

Cited by 52 publications

References 43 publications

Products of theEscherichia coliAcid Fitness Island Attenuate Metabolite Stress at Extremely Low pH and Mediate a Cell Density-Dependent Acid Resistance

Products of theEscherichia coliAcid Fitness Island Attenuate Metabolite Stress at Extremely Low pH and Mediate a Cell Density-Dependent Acid Resistance

Role of the Multidrug Resistance Regulator MarA in Global Regulation of the hdeAB Acid Resistance Operon in Escherichia coli

Mechanisms of Transcription Activation Exerted by GadX and GadW at the gadA and gadBC Gene Promoters of the Glutamate-Based Acid Resistance System in Escherichia coli

Contact Info

Product

Resources

About