Response regulator ArcA of Salmonella enterica serovar Typhimurium downregulates expression of OmpD, a porin facilitating uptake of hydrogen peroxide

ABSTRACTThe production of type 1 fimbriae inSalmonella entericaserovar Typhimurium is controlled, in part, by three proteins, FimZ, FimY, and FimW. Amino acid sequence analysis indicates that FimZ belongs to the family of bacterial response regulators of two-component systems. In these studies, we have demonstrated that introducing a mutation mimicking phosphorylation of FimZ is necessary for activation of its target gene,fimA. In addition, the interaction of FimZ with FimW, a repressor offimAexpression, occurs only when FimZ is phosphorylated. Consequently, the negative regulatory effect of FimW is most likely due to downmodulation of the active FimZ protein. FimY does not appear to function as a response regulator, and its activity can be lost by mimicking the phosphorylation of FimY. Overproduction of FimY cannot alleviate the nonfimbriate phenotype in a FimZ mutant, whereas high levels of FimZ can overcome the nonfimbriate phenotype of a FimY mutant. It appears that FimY acts upstream of FimZ to activatefimAexpression.

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A Salmonella enterica Serovar Typhimurium hemA Mutant Is Highly Susceptible to Oxidative DNA Damage

Journal of Bacteriology ◽

10.1128/jb.184.14.3774-3784.2002 ◽

2002 ◽

Vol 184 (14) ◽

pp. 3774-3784 ◽

Cited By ~ 30

Author(s):

Maya Elgrably-Weiss ◽

Sunny Park ◽

Eliana Schlosser-Silverman ◽

Ilan Rosenshine ◽

James Imlay ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Dna Damage ◽

Salmonella Enterica ◽

Fenton Reaction ◽

Oxidative Dna Damage ◽

Salmonella Enterica Serovar Typhimurium ◽

Mrna Levels ◽

Dependent Manner ◽

Intracellular Iron ◽

Serovar Typhimurium

ABSTRACT The first committed step in the biosynthesis of heme, an important cofactor of two catalases and a number of cytochromes, is catalyzed by the hemA gene product. Salmonella enterica serovar Typhimurium hemA26::Tn10d (hemA26) was identified in a genetic screen of insertion mutants that were sensitive to hydrogen peroxide. Here we show that the hemA26 mutant respires at half the rate of wild-type cells and is highly susceptible to the effects of oxygen species. Exposure of the hemA26 strain to hydrogen peroxide results in extensive DNA damage and cell death. The chelation of intracellular free iron fully abrogates the sensitivity of this mutant, indicating that the DNA damage results from the iron-catalyzed formation of hydroxyl radicals. The inactivation of heme synthesis does not change the amount of intracellular iron, but by diminishing the rate of respiration, it apparently increases the amount of reducing equivalents available to drive the Fenton reaction. We also report that hydrogen peroxide has opposite effects on the expression of hemA and hemH, the first and last genes of heme biosynthesis pathway, respectively. hemA mRNA levels decrease, while the transcription of hemH is induced by hydrogen peroxide, in an oxyR-dependent manner. The oxyR-dependent induction is suppressed under conditions that accelerate the Fenton reaction by a mechanism that is not yet understood.

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The Lactic Acid-Induced Acid Tolerance Response in Salmonella enterica Serovar Typhimurium Induces Sensitivity to Hydrogen Peroxide

Applied and Environmental Microbiology ◽

10.1128/aem.00538-06 ◽

2006 ◽

Vol 72 (8) ◽

pp. 5623-5625 ◽

Cited By ~ 22

Author(s):

E. J. Greenacre ◽

S. Lucchini ◽

J. C. D. Hinton ◽

T. F. Brocklehurst

Keyword(s):

Hydrogen Peroxide ◽

Lactic Acid ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhimurium ◽

Acid Tolerance ◽

Down Regulation ◽

Acid Tolerance Response ◽

Essential Component ◽

Serovar Typhimurium ◽

Tolerance Response

ABSTRACT Transcriptome analyses of Salmonella enterica serovar Typhimurium revealed that 15 genes were significantly up-regulated after 2 h of adaptation with lactic acid. cadB was the most highly up-regulated gene and was shown to be an essential component. Lactic acid-adapted cells exhibited sensitivity to hydrogen peroxide, likely due to down-regulation of the OxyR regulon.

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Salmonella enterica Serovar Typhimurium DT104 Displays a Rugose Phenotype

Applied and Environmental Microbiology ◽

10.1128/aem.67.9.4048-4056.2001 ◽

2001 ◽

Vol 67 (9) ◽

pp. 4048-4056 ◽

Cited By ~ 68

Author(s):

Yuda A. Anriany ◽

Ronald M. Weiner ◽

Judith A. Johnson ◽

Christian E. De Rezende ◽

Sam W. Joseph

Keyword(s):

Oxidative Stress ◽

Electron Microscopy ◽

Hydrogen Peroxide ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhimurium ◽

Low Ph ◽

Serovar Typhimurium ◽

Extracellular Substances ◽

Capsular Material ◽

Scanning Electron

ABSTRACT Rugose phenotypes, such as those observed in Vibrio cholerae, have increased resistance to chlorine, oxidative stress, and complement-mediated killing. In this study we identified and defined a rugose phenotype in Salmonella entericaserovar Typhimurium DT104 and showed induction only on certain media at 25°C after 3 days of incubation. Incubation at 37°C resulted in the appearance of the smooth phenotype. Observation of the ultrastructure of the rugose form and a stable smooth variant (Stv), which was isolated following a series of passages of the rugose cells, revealed extracellular substances only in cells from the rugose colony. Observation of the extracellular substance by scanning electron microscopy (SEM) was correlated with the appearance of corrugation during development of rugose colony morphology over a 4-day incubation period at 25°C. In addition, the cells also formed a pellicle in liquid broth, which was associated with the appearance of interlacing slime and fibrillar structures, as observed by SEM. The pellicle-forming cells were completely surrounded by capsular material, which bound cationic ferritin, thus indicating the presence of an extracellular anionic component. The rugose cells, in contrast to Stv, showed resistance to low pH and hydrogen peroxide and an ability to form biofilms. Based on these results and analogy to the rugose phenotype in V. cholerae, we propose a possible role for the rugose phenotype in the survival of S. enterica serovar Typhimurium DT104.

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Role of cpxA Mutations in the Resistance to Aminoglycosides and β-Lactams in Salmonella enterica serovar Typhimurium

Frontiers in Microbiology ◽

10.3389/fmicb.2021.604079 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wenxian Jing ◽

Juan Liu ◽

Shanshan Wu ◽

Xuerui Li ◽

Yongsheng Liu

Keyword(s):

Salmonella Enterica ◽

Deletion Mutant ◽

Salmonella Enterica Serovar Typhimurium ◽

Response Regulator ◽

Deletion Mutants ◽

Expression Levels ◽

Serovar Typhimurium ◽

Regulatory Effects ◽

A Site

Although it has been reported that deletion of the response regulator, CpxR, in the CpxRA system confers sensitivity to aminoglycosides (AGAs) and β-lactams in Salmonella enterica serovar Typhimurium, the regulatory effects of CpxA on multidrug resistance (MDR) are yet to be fully investigated in this organism. Here, to explore the role of CpxA in MDR, various cpxA mutants including a null mutant (JSΔcpxA), a site-directed mutant (JSΔcpxA38) and an internal in-frame deletion mutant (JSΔcpxA92–104) of the S. enterica serovar Typhimurium strain JS, were constructed. It was revealed that cpxA and cpxR deletion mutants have opposing roles in the regulation of resistance to AGAs and β-lactams. Amikacin and cefuroxime can activate the CpxRA system, which results in increased resistance of the wild-type compared with the cpxR deletion mutant. All the cpxA mutations significantly increased resistance to AGAs and β-lactams due to CpxRA system activation via the phosphorylation of CpxR. Moreover, AckA-Pta-dependent activation of CpxR increased the antibiotic resistance of cpxA deletion mutants. Further research revealed that the AcrAB-TolC conferred resistance to some AGAs and β-lactams but does not influence the regulation of resistance by CpxRA against these antibiotics. The detection of candidate MDR-related CpxR regulons revealed that the mRNA expression levels of spy, ycca, ppia, htpX, stm3031, and acrD were upregulated and that of ompW was downregulated in various cpxA mutants. Furthermore, the expression levels of nuoA and sdhC mRNAs were downregulated only in JSΔcpxA92–104. These results suggested that cpxA mutations contribute to AGAs and β-lactams resistance, which is dependent on CpxR.

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Role of Salmonella enterica Serovar Typhimurium Two-Component System PreA/PreB in Modulating PmrA-Regulated Gene Transcription

Journal of Bacteriology ◽

10.1128/jb.188.1.141-149.2006 ◽

2006 ◽

Vol 188 (1) ◽

pp. 141-149 ◽

Cited By ~ 32

Author(s):

Massimo Merighi ◽

Amanda Carroll-Portillo ◽

Alecia N. Septer ◽

Aditi Bhatiya ◽

John S. Gunn

Keyword(s):

Salmonella Enterica ◽

Target Genes ◽

Salmonella Enterica Serovar Typhimurium ◽

Response Regulator ◽

Polymyxin B ◽

Response Regulators ◽

Two Component System ◽

Component System ◽

Two Component ◽

Serovar Typhimurium

ABSTRACT The PmrA/PmrB two-component system encoded by the pmrCAB operon regulates the modification of Salmonella enterica serovar Typhimurium lipopolysaccharide leading to polymyxin B resistance. PmrA and PhoP are the only known activators of pmrCAB. A transposon mutagenesis screen for additional regulators of a pmrC::MudJ fusion led to the identification of a two-component system, termed PreA/PreB (pmrCAB regulators A and B), that controls the transcription of the pmrCAB operon in response to unknown signals. The initial observations indicated that insertions in, or a deletion of, the preB sensor, but not the preA response regulator, caused upregulation of pmrCAB. Interestingly, the expression of pmrCAB was not upregulated in a preAB mutant grown in LB broth, implicating PreA in the increased expression of pmrCAB in the preB strain. This was confirmed by overexpression of preA + in preAB or preB backgrounds, which resulted in significant upregulation or further upregulation of pmrCAB. No such effect was observed in any tested preB + backgrounds. Additionally, an ectopic construct expressing a preA[D51A] allele also failed to upregulate pmrC in any of the pre backgrounds tested, which implies that there is a need for phosphorylation in the activation of the target genes. The observed upregulation of pmrCAB occurred independently of the response regulators PmrA and PhoP. Although a preB mutation led to increased transcription of pmrCAB, this did not result in a measurable effect on polymyxin B resistance. Our genetic data support a model of regulation whereby, in response to unknown signals, the PreB sensor activates PreA, which in turn indirectly upregulates pmrCAB transcription.

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