The unphosphorylated form of the PilR two-component system regulates pilA gene expression in Geobacter sulfurreducens

2016 ◽  
Vol 24 (33) ◽  
pp. 25693-25701 ◽  
Author(s):  
Alberto Hernández-Eligio ◽  
Ángel Andrade ◽  
Lizeth Soto ◽  
Enrique Morett ◽  
Katy Juárez
Keyword(s):  
Gene Expression ◽  
Geobacter Sulfurreducens ◽  
Two Component System ◽  
Component System ◽  
Two Component ◽  
Pila Gene

scholarly journals Nutritional Regulation of the Sae Two-Component System by CodY inStaphylococcus aureus

2018 ◽  
Vol 200 (8) ◽  
Author(s):  
Kevin D. Mlynek ◽  
William E. Sause ◽  
Derek E. Moormeier ◽  
Marat R. Sadykov ◽  
Kurt R. Hill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virulence Factors ◽  
Virulence Gene ◽  
Nutrient Depletion ◽  
Global Regulator ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Two Component

ABSTRACTStaphylococcus aureussubverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via theS. aureusexoprotein expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease (nuc) gene expression via SaeR/S, but the mechanism remained unknown. Here, we identified two CodY binding motifs upstream of thesaeP1 promoter, which suggested direct regulation by this global regulator. We show that CodY shares a binding site with the positive activator SaeR and that alleviating direct CodY repression at this site is sufficient to abrogate stochastic expression, suggesting that CodY repressessaeexpression by blocking SaeR binding. Epistasis experiments support a model that CodY also controlssaeindirectly through Agr and Rot-mediated repression of thesaeP1 promoter. We also demonstrate that CodY repression ofsaerestrains production of secreted cytotoxins that kill human neutrophils. We conclude that CodY plays a previously unrecognized role in controlling virulence gene expression via SaeR/S and suggest a mechanism by which CodY acts as a master regulator of pathogenesis by tying nutrient availability to virulence gene expression.IMPORTANCEBacterial mechanisms that mediate the switch from a commensal to pathogenic lifestyle are among the biggest unanswered questions in infectious disease research. Since the expression of most virulence genes is often correlated with nutrient depletion, this implies that virulence is a response to the lack of nourishment in host tissues and that pathogens likeS. aureusproduce virulence factors in order to gain access to nutrients in the host. Here, we show that specific nutrient depletion signals appear to be funneled to the SaeR/S system through the global regulator CodY. Our findings reveal a strategy by whichS. aureusdelays the production of immune evasion and immune-cell-killing proteins until key nutrients are depleted.

scholarly journals Transcriptome Profiling and Functional Analysis of Agrobacterium tumefaciens Reveals a General Conserved Response to Acidic Conditions (pH 5.5) and a Complex Acid-Mediated Signaling Involved in Agrobacterium-Plant Interactions

2007 ◽  
Vol 190 (2) ◽  
pp. 494-507 ◽  
Author(s):  
Ze-Chun Yuan ◽  
Pu Liu ◽  
Panatda Saenkham ◽  
Kathleen Kerr ◽  
Eugene W. Nester
Keyword(s):  
Gene Expression ◽  
Agrobacterium Tumefaciens ◽  
Expression Patterns ◽  
Dna Transfer ◽  
Plant Interactions ◽  
Type Vi Secretion System ◽  
Two Component System ◽  
Component System ◽  
Two Component ◽  
Acidic Conditions

ABSTRACT Agrobacterium tumefaciens transferred DNA (T-DNA) transfer requires that the virulence genes (vir regulon) on the tumor-inducing (Ti) plasmid be induced by plant phenolic signals in an acidic environment. Using transcriptome analysis, we found that these acidic conditions elicit two distinct responses: (i) a general and conserved response through which Agrobacterium modulates gene expression patterns to adapt to environmental acidification and (ii) a highly specialized acid-mediated signaling response involved in Agrobacterium-plant interactions. Overall, 78 genes were induced and 74 genes were repressed significantly under acidic conditions (pH 5.5) compared to neutral conditions (pH 7.0). Microarray analysis not only confirmed previously identified acid-inducible genes but also uncovered many new acid-induced genes which may be directly involved in Agrobacterium-plant interactions. These genes include virE0, virE1, virH1, and virH2. Further, the chvG-chvI two-component system, previously shown to be critical for virulence, was also induced under acid conditions. Interestingly, acidic conditions induced a type VI secretion system and a putative nonheme catalase. We provide evidence suggesting that acid-induced gene expression was independent of the VirA-VirG two-component system. Our results, together with previous data, support the hypothesis that there is three-step sequential activation of the vir regulon. This process involves a cascade regulation and hierarchical signaling pathway featuring initial direct activation of the VirA-VirG system by the acid-activated ChvG-ChvI system. Our data strengthen the notion that Agrobacterium has evolved a mechanism to perceive and subvert the acidic conditions of the rhizosphere to an important signal that initiates and directs the early virulence program, culminating in T-DNA transfer.

scholarly journals Delineation of the pH-responsive regulon controlled by the Helicobacter pylori ArsRS two- component system

2021 ◽  
Author(s):  
John T. Loh ◽  
Miranda V. Shum ◽  
Scott D.R. Jossart ◽  
Anne M. Campbell ◽  
Neha Sawhney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Differentially Expressed ◽  
Sensor Kinase ◽  
Ph Responsive ◽  
Two Component System ◽  
Component System ◽  
Wide Range ◽  
Two Component ◽  
H Pylori

Helicobacter pylori encounters a wide range of pH within the human stomach. In a comparison of H. pylori cultured in vitro under neutral or acidic conditions, about 15% of genes are differentially expressed, and corresponding changes are detectable for many of the encoded proteins. The ArsRS two-component system (TCS), comprised of the sensor kinase ArsS and its cognate response regulator ArsR, has an important role in mediating pH-responsive changes in H. pylori gene expression. In this study, we sought to delineate the pH-responsive ArsRS regulon and further define the role of ArsR in pH-responsive gene expression. We compared H. pylori strains containing an intact ArsRS system with an arsS null mutant or strains containing site-specific mutations of a conserved aspartate residue (D52) in ArsR, which is phosphorylated in response to signals relayed by the cognate sensor kinase ArsS. We identified 178 genes that were pH-responsive in strains containing an intact ArsRS system but not in ΔarsS or arsR mutants. These constituents of the pH-responsive ArsRS regulon include genes involved in acid acclimatization (ureAB, amidases), oxidative stress responses (katA, sodB), transcriptional regulation related to iron or nickel homeostasis (fur, nikR), and genes encoding outer membrane proteins [including sabA, alpA, alpB, hopD (labA), and horA]. When comparing H. pylori strains containing an intact ArsRS TCS with arsRS mutants, each cultured at neutral pH, relatively few genes are differentially expressed. Collectively, these data suggest that ArsRS-mediated gene regulation has an important role in H. pylori adaptation to changing pH conditions.

scholarly journals The NarX-NarL two-component system is a global regulator of biofilm formation, natural product biosynthesis, and host-associated survival in Burkholderia pseudomallei

2020 ◽  
Author(s):  
Mihnea R. Mangalea ◽  
Bradley R. Borlee
Keyword(s):  
Gene Expression ◽  
Surface Waters ◽  
Biofilm Formation ◽  
Burkholderia Pseudomallei ◽  
Nitrosative Stress ◽  
Two Component System ◽  
Component System ◽  
Sensing System ◽  
Two Component ◽  
Nitrate And Nitrite

AbstractIn the environment, Burkholderia pseudomallei exists as a saprophyte inhabiting soils and surface waters where denitrification is important for anaerobic respiration. As an opportunistic pathogen, B. pseudomallei transitions from the environment to infect human and animal hosts where respiratory nitrate reduction enables replication in anoxic conditions. We have previously shown that B. pseudomallei responds to nitrate and nitrite in part by inhibiting biofilm formation and altering cyclic di-GMP signaling. Here, we describe the global transcriptomic response to nitrate and nitrite to characterize the nitrosative stress response relative to biofilm inhibition. To better understand the roles of nitrate-sensing in the biofilm inhibitory phenotype of B. pseudomallei, we created in-frame deletions of narX (Bp1026b_I1014) and narL (Bp1026b_I1013), which are adjacent components of the conserved nitrate-sensing two-component system. Through differential expression analysis of RNA-seq data, we observed that key components of the biofilm matrix are downregulated in response to nitrate and nitrite. In addition, several gene loci associated with the stringent response, central metabolism dysregulation, antibiotic tolerance, and pathogenicity determinants were significantly altered in their expression. Some of the most differentially expressed genes were nonribosomal peptide synthases (NRPS) and/or polyketide synthases (PKS) encoding the proteins for the biosynthesis of bactobolin, malleilactone, and syrbactin, in addition to an uncharacterized cryptic NRPS biosynthetic cluster. We also observed reduced expression of ribosomal structural and biogenesis loci, and gene clusters associated with translation and DNA replication, indicating modulation of growth rate and metabolism under nitrosative stress conditions. The differences in expression observed under nitrosative stress were reversed in narX and narL mutants, suggesting that nitrate sensing is an important checkpoint for regulating the diverse metabolic changes occurring in the biofilm inhibitory phenotype. Moreover, in a macrophage model of infection, narX and narL mutants were attenuated in intracellular replication, suggesting that nitrate sensing is important for host survival.Author SummaryBurkholderia pseudomallei is a saprophytic bacterium inhabiting soils and surface waters throughout the tropics causing severe disease in humans and animals. Environmental signals such as the accumulation of inorganic ions mediates the biofilm forming capabilities and survival of B. pseudomallei. In particular, nitrate metabolism inhibits B. pseudomallei biofilm formation through complex regulatory cascades that relay environmental cues to intracellular second messengers that modulate bacterial physiology. Nitrates are common environmental contaminants derived from artificial fertilizers and byproducts of animal wastes that can be readily reduced by bacteria capable of denitrification. In B. pseudomallei 1026b, biofilm dynamics are in part regulated by a gene pathway involved in nitrate sensing, metabolism, and transport. This study investigated the role of a two-component nitrate sensing system, NarX-NarL, in regulating gene expression, biofilm formation, and cellular invasion. Global gene expression analyses in the wild type, as compared to Δ narX and Δ narL mutant strains with nitrate or nitrite implicate the NarX-NarL system in the regulation of biofilm components as well as B. pseudomallei host-associated survival. This study characterizes a conserved nitrate sensing system that is important in environmental and host-associated contexts and aims to bridge a gap between these two important B. pseudomallei lifestyles.

Protein A gene expression is regulated by DNA supercoiling which is modified by the ArlS–ArlR two-component system of Staphylococcus aureus

Microbiology ◽  
2004 ◽  
Vol 150 (11) ◽  
pp. 3807-3819 ◽  
Author(s):  
Bénédicte Fournier ◽  
André Klier
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Virulence Genes ◽  
Protein A ◽  
Dna Gyrase ◽  
Dna Supercoiling ◽  
Two Component System ◽  
Component System ◽  
High Osmolarity ◽  
Two Component

Bacterial pathogens such as Staphylococcus aureus undergo major physiological changes when they infect their hosts, requiring the coordinated regulation of gene expression in response to the stresses encountered. Several environmental factors modify the expression of S. aureus virulence genes. This report shows that the expression of spa (virulence gene encoding the cell-wall-associated protein A) is down-regulated by high osmolarity (1 M NaCl, 1 M KCl or 1 M sucrose) in the wild-type strain and upregulated by novobiocin (a DNA gyrase inhibitor that relaxes DNA). A gyrB142 allele corresponding to a double mutation in the B subunit of DNA gyrase relaxed DNA and consequently induced spa expression, confirming that spa expression is regulated by DNA topology. Furthermore, in the presence of novobiocin plus 1 M NaCl, a good correlation was observed between DNA supercoiling and spa expression. The ArlS–ArlR two-component system is involved in the expression of virulence genes such as spa. Presence of an arlRS deletion decreased the effect of DNA supercoiling modulators on spa expression, suggesting that active Arl proteins are necessary for the full effect of DNA gyrase inhibitors and high osmolarity on spa expression. Indeed, evidence is provided for a relationship between the arlRS deletion and topological changes in plasmid DNA.

scholarly journals A novel copper-sensing two-component system for inducing Dsb gene expression in bacteria

2021 ◽  
Author(s):  
Liang Yu ◽  
Qiao Cao ◽  
Weizhong Chen ◽  
Nana Yang ◽  
Cai-Guang Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Two Component System ◽  
Component System ◽  
Two Component

scholarly journals ThePseudomonas aeruginosaPilSR Two-Component System Regulates Both Twitching and Swimming Motilities

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Sara L. N. Kilmury ◽  
Lori L. Burrows
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iv Pili ◽  
Geobacter Sulfurreducens ◽  
Type Iv Pilus ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Swimming Motility ◽  
Type Iv ◽  
Two Component

ABSTRACTMotility is an important virulence trait for many bacterial pathogens, allowing them to position themselves in appropriate locations at appropriate times. The motility structures type IV pili and flagella are also involved in sensing surface contact, which modulates pathogenicity. InPseudomonas aeruginosa, the PilS-PilR two-component system (TCS) regulates expression of the type IV pilus (T4P) major subunit PilA, while biosynthesis of the single polar flagellum is regulated by a hierarchical system that includes the FleSR TCS. Previous studies ofGeobacter sulfurreducensandDichelobacter nodosusimplicated PilR in regulation of non-T4P-related genes, including some involved in flagellar biosynthesis. Here we used transcriptome sequencing (RNA-seq) analysis to identify genes in addition topilAwith changes in expression in the absence ofpilR. Among the genes identified were 10 genes whose transcription increased in thepilAmutant but decreased in thepilRmutant, despite both mutants lacking T4P and pilus-related phenotypes. The products of these inversely dysregulated genes, many of which were hypothetical, may be important for virulence and surface-associated behaviors, as mutants had altered swarming motility, biofilm formation, type VI secretion system expression, and pathogenicity in a nematode model. Further, the PilSR TCS positively regulated transcription offleSR, and thus many genes in the FleSR regulon. As a result,pilSRdeletion mutants had defects in swimming motility that were independent of the loss of PilA. Together, these data suggest that in addition to controlling T4P expression, PilSR could have a broader role in the regulation ofP. aeruginosamotility and surface sensing behaviors.IMPORTANCESurface appendages such as type IV pili and flagella are important for establishing surface attachment and infection in a host in response to appropriate cues. The PilSR regulatory system that controls type IV pilus expression inPseudomonas aeruginosahas an established role in expression of the major pilin PilA. Here we provide evidence supporting a new role for PilSR in regulating flagellum-dependent swimming motility in addition to pilus-dependent twitching motility. Further, even though bothpilAandpilRmutants lack PilA and pili, we identified sets of genes downregulated in thepilRmutant and upregulated in apilAmutant as well as genes downregulated only in apilRmutant, independent of pilus expression. This finding suggests that change in the inner membrane levels of PilA is only one of the cues to which PilR responds to modulate gene expression. Identification of PilR as a regulator of multiple motility pathways may make it an interesting therapeutic target for antivirulence compounds.

DnaJ and ClpX are required for HitRS and HssRS two-component system signaling in Bacillus anthracis

2021 ◽  
Author(s):  
Clare L. Laut ◽  
Catherine S. Leasure ◽  
Hualiang Pi ◽  
Sophia M. Carlin ◽  
Michelle L. Chu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Bacillus Anthracis ◽  
Cell Envelope ◽  
Genetic Selection ◽  
Selection Strategy ◽  
Two Component System ◽  
Component System ◽  
Two Component ◽  
Substantial Risk

Bacillus anthracis is the causative agent of anthrax. This Gram-positive bacterium poses a substantial risk to human health due to high mortality rates and the potential for malicious use as a bioterror weapon. To survive within the vertebrate host, B. anthracis relies on two-component system (TCS) signaling to sense host-induced stresses and respond to alterations in the environment through changes in target gene expression. HitRS and HssRS are cross-regulating TCSs in B. anthracis that respond to cell envelope disruptions and high heme levels, respectively. In this study, an unbiased and targeted genetic selection was designed to identify gene products that are involved in HitRS and HssRS signaling. This selection led to the identification of inactivating mutations within dnaJ and clpX that disrupt HitRS- and HssRS-dependent gene expression. DnaJ and ClpX are the substrate-binding subunits of the DnaJK protein chaperone and ClpXP protease, respectively. DnaJ regulates the levels of HitR and HitS to facilitate signal transduction, while ClpX specifically regulates HitS levels. Together these results reveal that the protein homeostasis regulators, DnaJ and ClpX, function to maintain B. anthracis signal transduction activities through TCS regulation. One sentence summary: Use of a genetic selection strategy to identify modulators of two-component system signaling in Bacillus anthracis .

Sign in / Sign up

Export Citation Format

Share Document