scholarly journals The Rcs System in Enterobacteriaceae: Envelope Stress Responses and Virulence Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiao Meng ◽  
Glenn Young ◽  
Jingyu Chen
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Cell Envelope ◽  
Regulatory System ◽  
Virulence Regulation ◽  
Bacterial Interaction ◽  
Envelope Stress

The bacterial cell envelope is a protective barrier at the frontline of bacterial interaction with the environment, and its integrity is regulated by various stress response systems. The Rcs (regulator of capsule synthesis) system, a non-orthodox two-component regulatory system (TCS) found in many members of the Enterobacteriaceae family, is one of the envelope stress response pathways. The Rcs system can sense envelope damage or defects and regulate the transcriptome to counteract stress, which is particularly important for the survival and virulence of pathogenic bacteria. In this review, we summarize the roles of the Rcs system in envelope stress responses (ESRs) and virulence regulation. We discuss the environmental and intrinsic sources of envelope stress that cause activation of the Rcs system with an emphasis on the role of RcsF in detection of envelope stress and signal transduction. Finally, the different regulation mechanisms governing the Rcs system’s control of virulence in several common pathogens are introduced. This review highlights the important role of the Rcs system in the environmental adaptation of bacteria and provides a theoretical basis for the development of new strategies for control, prevention, and treatment of bacterial infections.

scholarly journals Regulation of Flagellum Biosynthesis in Response to Cell Envelope Stress inSalmonella entericaSerovar Typhimurium

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Imke Spöring ◽  
Sebastian Felgner ◽  
Matthias Preuße ◽  
Denitsa Eckweiler ◽  
Manfred Rohde ◽  
...  
Keyword(s):  
Immune System ◽  
Stress Response ◽  
Pathogenic Bacteria ◽  
Cell Envelope ◽  
Membrane Integrity ◽  
Flagellar Biosynthesis ◽  
Envelope Stress ◽  
Flagellum Biosynthesis ◽  
Hostile Environments ◽  
Prime Target

ABSTRACTFlagellum-driven motility ofSalmonella entericaserovar Typhimurium facilitates host colonization. However, the large extracellular flagellum is also a prime target for the immune system. As consequence, expression of flagella is bistable within a population ofSalmonella, resulting in flagellated and nonflagellated subpopulations. This allows the bacteria to maximize fitness in hostile environments. The degenerate EAL domain protein RflP (formerly YdiV) is responsible for the bistable expression of flagella by directing the flagellar master regulatory complex FlhD4C2with respect to proteolytic degradation. Information concerning the environmental cues controlling expression ofrflPand thus about the bistable flagellar biosynthesis remains ambiguous. Here, we demonstrated that RflP responds to cell envelope stress and alterations of outer membrane integrity. Lipopolysaccharide (LPS) truncation mutants ofSalmonellaTyphimurium exhibited increasing motility defects due to downregulation of flagellar gene expression. Transposon mutagenesis and genetic profiling revealed that σ24(RpoE) and Rcs phosphorelay-dependent cell envelope stress response systems sense modifications of the lipopolysaccaride, low pH, and activity of the complement system. This subsequently results in activation of RflP expression and degradation of FlhD4C2via ClpXP. We speculate that the presence of diverse hostile environments inside the host might result in cell envelope damage and would thus trigger the repression of resource-costly and immunogenic flagellum biosynthesis via activation of the cell envelope stress response.IMPORTANCEPathogenic bacteria such asSalmonellaTyphimurium sense and adapt to a multitude of changing and stressful environments during host infection. At the initial stage of gastrointestinal colonization,Salmonellauses flagellum-mediated motility to reach preferred sites of infection. However, the flagellum also constitutes a prime target for the host’s immune response. Accordingly, the pathogen needs to determine the spatiotemporal stage of infection and control flagellar biosynthesis in a robust manner. We found thatSalmonellauses signals from cell envelope stress-sensing systems to turn off production of flagella. We speculate that downregulation of flagellum synthesis after cell envelope damage in hostile environments aids survival ofSalmonelladuring late stages of infection and provides a means to escape recognition by the immune system.

scholarly journals Alternative Sigma Factor RpoE Is Important for Vibrio parahaemolyticus Cell Envelope Stress Response and Intestinal Colonization

2014 ◽  
Vol 82 (9) ◽  
pp. 3667-3677 ◽  
Author(s):  
Brandy Haines-Menges ◽  
W. Brian Whitaker ◽  
E. Fidelma Boyd
Keyword(s):  
Stress Response ◽  
Vibrio Parahaemolyticus ◽  
Response Regulator ◽  
Cell Envelope ◽  
Polymyxin B ◽  
Content Type ◽  
Alternative Sigma Factors ◽  
Envelope Stress

ABSTRACTVibrio parahaemolyticusis a halophile that inhabits brackish waters and a wide range of hosts, including crustaceans, fish, mollusks, and humans. In humans, it is the leading cause of bacterial seafood-borne gastroenteritis. The focus of this work was to determine the role of alternative sigma factors in the stress response ofV. parahaemolyticusRIMD2210633, an O3:K6 pandemic isolate. Bioinformatics identified five putative extracytoplasmic function (ECF) family of alternative sigma factors: VP0055, VP2210, VP2358, VP2578, and VPA1690. ECF factors typically respond to cell wall/cell envelope stress, iron levels, and the oxidation state of the cell. We have demonstrated here that one such sigma factor, VP2578, a homologue of RpoE fromEscherichia coli, is important for survival under a number of cell envelope stress conditions and in gastrointestinal colonization of a streptomycin-treated adult mouse. In this study, we determined that anrpoEdeletion mutant strain BHM2578 compared to the wild type (WT) was significantly more sensitive to polymyxin B, ethanol, and high-temperature stresses. We demonstrated that inin vivocompetition assays between therpoEmutant and the WT marked with the β-galactosidase genelacZ(WBWlacZ), the mutant strain was defective in colonization compared to the WT. In contrast, deletion of therpoSstress response regulator did not affectin vivosurvival. In addition, we examined the role of the outer membrane protein, OmpU, which inV. choleraeis proposed to be the sole activator of RpoE. We found that anompUdeletion mutant was sensitive to bile salt stress but resistant to polymyxin B stress, indicating OmpU is not essential for the cell envelope stress responses or RpoE function. Overall, these data demonstrate that RpoE is a key cell envelope stress response regulator and, similar toE. coli, RpoE may have several factors that stimulate its function.

scholarly journals Characterization of the CpxRA Regulon in Haemophilus ducreyi

2010 ◽  
Vol 78 (11) ◽  
pp. 4779-4791 ◽  
Author(s):  
Maria Labandeira-Rey ◽  
Chad A. Brautigam ◽  
Eric J. Hansen
Keyword(s):  
Stress Response ◽  
Response Regulator ◽  
Cell Envelope ◽  
Bacterial Species ◽  
Regulatory System ◽  
Promoter Regions ◽  
Mobility Shift ◽  
Envelope Stress ◽  
Two Component ◽  
Genes Encoding

ABSTRACT The H aemophilus ducreyi 35000HP genome encodes a homolog of the CpxRA two-component cell envelope stress response system originally characterized in E scherichia coli. CpxR, the cytoplasmic response regulator, was shown previously to be involved in repression of the expression of the lspB-lspA2 operon (M. Labandeira-Rey, J. R. Mock, and E. J. Hansen, Infect. Immun. 77:3402-3411, 2009). In the present study, the H. ducreyi CpxR and CpxA proteins were shown to closely resemble those of other well-studied bacterial species. A cpxA deletion mutant and a CpxR-overexpressing strain were used to explore the extent of the CpxRA regulon. DNA microarray and real-time reverse transcriptase (RT) PCR analyses indicated several potential regulatory targets for the H. ducreyi CpxRA two-component regulatory system. Electrophoretic mobility shift assays (EMSAs) were used to prove that H. ducreyi CpxR interacted with the promoter regions of genes encoding both known and putative virulence factors of H. ducreyi, including the lspB-lspA2 operon, the flp operon, and dsrA. Interestingly, the use of EMSAs also indicated that H. ducreyi CpxR did not bind to the promoter regions of several genes predicted to encode factors involved in the cell envelope stress response. Taken together, these data suggest that the CpxRA system in H. ducreyi, in contrast to that in E. coli, may be involved primarily in controlling expression of genes not involved in the cell envelope stress response.

scholarly journals The σE Cell Envelope Stress Response of Streptomyces coelicolor Is Influenced by a Novel Lipoprotein, CseA

2006 ◽  
Vol 188 (20) ◽  
pp. 7222-7229 ◽  
Author(s):  
Matthew I. Hutchings ◽  
Hee-Jeon Hong ◽  
Emmanuelle Leibovitz ◽  
Iain C. Sutcliffe ◽  
Mark J. Buttner
Keyword(s):  
Stress Response ◽  
Response Regulator ◽  
Cell Envelope ◽  
Streptomyces Coelicolor ◽  
Signal Transduction System ◽  
Two Component System ◽  
Positive Bacterium ◽  
Sensor Histidine Kinase ◽  
Envelope Stress

ABSTRACT We have investigated the role of CseA in the σE cell envelope stress response of the gram-positive bacterium Streptomyces coelicolor. σE is an extracytoplasmic function RNA polymerase sigma factor required for normal cell envelope integrity in S. coelicolor. σE is encoded within a four-gene operon that also encodes CseA, a protein of unknown function, CseB, a response regulator and CseC, a transmembrane sensor histidine kinase (Cse represents control of sigma E). Previous work has shown that transcription of the sigE gene is completely dependent on the CseBC two-component system and that the CseBC-σE signal transduction system is induced by a wide variety of cell-wall-damaging agents. Here we address the role of CseA, a protein with no homologues outside the streptomycetes. We show that CseA is a novel lipoprotein localized to the extracytoplasmic face of the cell membrane and that loss of CseA results in upregulation of the sigE promoter.

Genome-wide transcriptional profiling of the cell envelope stress response and the role of LisRK and CesRK in Listeria monocytogenes

Microbiology ◽  
2012 ◽  
Vol 158 (4) ◽  
pp. 963-974 ◽  
Author(s):  
Pia Kiil Nielsen ◽  
Ann Zahle Andersen ◽  
Maarten Mols ◽  
Stijn van der Veen ◽  
Tjakko Abee ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Stress Response ◽  
Cell Envelope ◽  
Transcriptional Profiling ◽  
Genome Wide ◽  
Envelope Stress

scholarly journals Circuitry Linking the Global Csr- and σE-Dependent Cell Envelope Stress Response Systems

2017 ◽  
Vol 199 (23) ◽  
Author(s):  
Helen Yakhnin ◽  
Robert Aichele ◽  
Sarah E. Ades ◽  
Tony Romeo ◽  
Paul Babitzke
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Translational Control ◽  
Sigma Factor ◽  
Rna Binding ◽  
Cell Envelope ◽  
Stringent Response ◽  
Content Type ◽  
Envelope Stress ◽  
Dependent Cell

ABSTRACT CsrA of Escherichia coli is an RNA-binding protein that globally regulates a wide variety of cellular processes and behaviors, including carbon metabolism, motility, biofilm formation, and the stringent response. CsrB and CsrC are small RNAs (sRNAs) that sequester CsrA, thereby preventing CsrA-mRNA interaction. RpoE (σE) is the extracytoplasmic stress response sigma factor of E. coli. Previous RNA sequencing (RNA-seq) studies identified rpoE mRNA as a CsrA target. Here, we explored the regulation of rpoE by CsrA and found that CsrA represses rpoE translation. Gel mobility shift, footprint, and toeprint studies identified three CsrA binding sites in the rpoE leader transcript, one of which overlaps the rpoE Shine-Dalgarno (SD) sequence, while another overlaps the rpoE translation initiation codon. Coupled in vitro transcription-translation experiments showed that CsrA represses rpoE translation by binding to these sites. We further demonstrate that σE indirectly activates the transcription of csrB and csrC, leading to increased sequestration of CsrA, such that repression of rpoE by CsrA is reduced. We propose that the Csr system fine-tunes the σE-dependent cell envelope stress response. We also identified a 51-amino-acid coding sequence whose stop codon overlaps the rpoE start codon and demonstrate that rpoE is translationally coupled with this upstream open reading frame (ORF51). The loss of coupling reduces rpoE translation by more than 50%. Identification of a translationally coupled ORF upstream of rpoE suggests that this previously unannotated protein may participate in the cell envelope stress response. In keeping with existing nomenclature, we named ORF51 rseD, resulting in an operon arrangement of rseD-rpoE-rseA-rseB-rseC. IMPORTANCE CsrA posttranscriptionally represses genes required for bacterial stress responses, including the stringent response, catabolite repression, and the RpoS (σS)-mediated general stress response. We show that CsrA represses the translation of rpoE, encoding the extracytoplasmic stress response sigma factor, and that σE indirectly activates the transcription of csrB and csrC, resulting in reciprocal regulation of these two global regulatory systems. These findings suggest that extracytoplasmic stress leads to derepression of rpoE translation by CsrA, and CsrA-mediated repression helps reset RpoE abundance to prestress levels once envelope damage is repaired. The discovery of an ORF, rseD, translationally coupled with rpoE adds further complexity to translational control of rpoE.

scholarly journals Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Shweta Devi ◽  
Vijay Kumar ◽  
Sandeep Kumar Singh ◽  
Ashish Kant Dubey ◽  
Jong-Joo Kim
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Neurodegenerative Disorders ◽  
Cell Damage ◽  
Cellular Stress ◽  
Clinical Manifestations ◽  
Cellular Stress Response ◽  
Dramatic Rise ◽  
Cellular Stress Responses

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

scholarly journals Epigenetic Targeting of Autophagy via HDAC Inhibition in Tumor Cells: Role of p53

2018 ◽  
Vol 19 (12) ◽  
pp. 3952 ◽  
Author(s):  
Maria Mrakovcic ◽  
Lauren Bohner ◽  
Marcel Hanisch ◽  
Leopold F. Fröhlich
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Histone Deacetylase ◽  
Stress Responses ◽  
Histone Deacetylase Inhibitors ◽  
Tumor Therapy ◽  
Regulatory System ◽  
Anticancer Activities ◽  
Mutational Status

Tumor development and progression is the consequence of genetic as well as epigenetic alterations of the cell. As part of the epigenetic regulatory system, histone acetyltransferases (HATs) and deacetylases (HDACs) drive the modification of histone as well as non-histone proteins. Derailed acetylation-mediated gene expression in cancer due to a delicate imbalance in HDAC expression can be reversed by histone deacetylase inhibitors (HDACi). Histone deacetylase inhibitors have far-reaching anticancer activities that include the induction of cell cycle arrest, the inhibition of angiogenesis, immunomodulatory responses, the inhibition of stress responses, increased generation of oxidative stress, activation of apoptosis, autophagy eliciting cell death, and even the regulation of non-coding RNA expression in malignant tumor cells. However, it remains an ongoing issue how tumor cells determine to respond to HDACi treatment by preferentially undergoing apoptosis or autophagy. In this review, we summarize HDACi-mediated mechanisms of action, particularly with respect to the induction of cell death. There is a keen interest in assessing suitable molecular factors allowing a prognosis of HDACi-mediated treatment. Addressing the results of our recent study, we highlight the role of p53 as a molecular switch driving HDACi-mediated cellular responses towards one of both types of cell death. These findings underline the importance to determine the mutational status of p53 for an effective outcome in HDACi-mediated tumor therapy.

scholarly journals Make and break the alarmone: regulation of (p)ppGpp synthetase/hydrolase enzymes in bacteria

2019 ◽  
Vol 43 (4) ◽  
pp. 389-400 ◽  
Author(s):  
Séverin Ronneau ◽  
Régis Hallez
Keyword(s):  
Cell Cycle ◽  
Stress Response ◽  
Stress Responses ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Second Messengers ◽  
Molecular Devices ◽  
Environmental Cues ◽  
Fluctuating Environments ◽  
Harsh Conditions

ABSTRACTBacteria use dedicated mechanisms to respond adequately to fluctuating environments and to optimize their chances of survival in harsh conditions. One of the major stress responses used by virtually all bacteria relies on the sharp accumulation of an alarmone, the guanosine penta- or tetra-phosphate commonly referred to as (p)ppGpp. Under stressful conditions, essentially nutrient starvation, these second messengers completely reshape the metabolism and physiology by coordinately modulating growth, transcription, translation and cell cycle. As a central regulator of bacterial stress response, the alarmone is also involved in biofilm formation, virulence, antibiotics tolerance and resistance in many pathogenic bacteria. Intracellular concentrations of (p)ppGpp are determined by a highly conserved and widely distributed family of proteins called RelA-SpoT Homologs (RSH). Recently, several studies uncovering mechanisms that regulate RSH activities have renewed a strong interest in this field. In this review, we outline the diversity of the RSH protein family as well as the molecular devices used by bacteria to integrate and transform environmental cues into intracellular (p)ppGpp levels.

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