Two-Component Signal Transduction System VraSR Contributes to Neuroinflammation in Streptococcus Suis Meningitis

Abstract Background: Streptococcus suis (S. suis) is an important zoonotic pathogen that can cause high morbidity and mortality in both humans and swine. As the most important life-threatening infection of the central nervous system (CNS), meningitis is an important symptom of S. suis infection. The VraSR is a critical two-component signal transduction system that affects S. suis ability to resist against host innate immune system and promotes the ability of S. suis to adhere to hBMEC. Whether and how VraSR contributes to the development of S. suis meningitis are currently unknown.Methods: The in vivo colonization, in vivo BBB permeability, histopathological examination and immunohistochemistry were applied to compare and characterize the degree of destruction of brain tissue in response to wild type SC19 and mutant ΔvraSR. Western blotting and real-time PCR were combined to identify the breakdown of tight junction proteins (TJ proteins). The secretion of proinflammatory cytokines and chemokines in the serum were detected on a BD FACSVerse flow cytometer.Results: We found an important role of VraSR regulatory system in S. suis SC19-induced meningitis. A mouse infection model demonstrated that ΔvraSR had significantly attenuated inflammatory lesions in the brain tissues compared with wild-type S. suis. In vitro, we characterized that SC19 could increase the blood-brain barrier (BBB) permeability through downregulating the TJ proteins compared with mutant ΔvraSR. Moreover, we found significant generation of proinflammatory cytokines and chemokines in the serum including IL-6, TNF-α, MCP-1, and IL-12p70 compared with ΔvraSR infected mice.Conclusions: For the first time, our work investigated the VraSR regulatory system of S. suis played an important role in streptococcal meningitis and revealed VraSR to be an important contributor to the disruption of TJ proteins. Characterization of these BBB disruption will facilitate further study of meningitis mechanisms in humans, thereby offering the development of novel preventative and therapeutic strategies against infection with S. suis.

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Analysis of Protein Expression Regulated by the Helicobacter pylori ArsRS Two-Component Signal Transduction System

Journal of Bacteriology ◽

10.1128/jb.01703-08 ◽

2010 ◽

Vol 192 (8) ◽

pp. 2034-2043 ◽

Cited By ~ 29

Author(s):

John T. Loh ◽

Shobhana S. Gupta ◽

David B. Friedman ◽

Andrzej M. Krezel ◽

Timothy L. Cover

Keyword(s):

Signal Transduction ◽

Helicobacter Pylori ◽

Protein Expression ◽

Thioredoxin Reductase ◽

Acid Resistance ◽

Wild Type ◽

Signal Transduction System ◽

Promoter Regions ◽

Two Component ◽

Two Component Signal Transduction

ABSTRACT Previous studies have shown that the Helicobacter pylori ArsRS two-component signal transduction system contributes to acid-responsive gene expression. To identify additional members of the ArsRS regulon and further investigate the regulatory role of the ArsRS system, we analyzed protein expression in wild-type and arsS null mutant strains. Numerous proteins were differentially expressed in an arsS mutant strain compared to a wild-type strain when the bacteria were cultured at pH 5.0 and also when they were cultured at pH 7.0. Genes encoding 14 of these proteins were directly regulated by the ArsRS system, based on observed binding of ArsR to the relevant promoter regions. The ArsRS-regulated proteins identified in this study contribute to acid resistance (urease and amidase), acetone metabolism (acetone carboxylase), resistance to oxidative stress (thioredoxin reductase), quorum sensing (Pfs), and several other functions. These results provide further definition of the ArsRS regulon and underscore the importance of the ArsRS system in regulating expression of H. pylori proteins during bacterial growth at both neutral pH and acidic pH.

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The CpxRA Two-Component System Is Essential for Citrobacter rodentium Virulence

Infection and Immunity ◽

10.1128/iai.00194-15 ◽

2015 ◽

Vol 83 (5) ◽

pp. 1919-1928 ◽

Cited By ~ 17

Author(s):

Jenny-Lee Thomassin ◽

Natalia Giannakopoulou ◽

Lei Zhu ◽

Jeremy Gross ◽

Kristiana Salmon ◽

...

Keyword(s):

Signal Transduction ◽

Infection Model ◽

Citrobacter Rodentium ◽

Human Pathogens ◽

Signal Transduction System ◽

Content Type ◽

E Coli ◽

Two Component ◽

Two Component Signal Transduction

Citrobacter rodentiumis a murine intestinal pathogen used as a model for the foodborne human pathogens enterohemorrhagicEscherichia coliand enteropathogenicE. coli. During infection, these pathogens use two-component signal transduction systems to detect and adapt to changing environmental conditions. InE. coli, the CpxRA two-component signal transduction system responds to envelope stress by modulating the expression of a myriad of genes. Quantitative real-time PCR showed thatcpxRAwas expressed in the colon of C57BL/6J mice infected withC. rodentium. To determine whether CpxRA plays a role duringC. rodentiuminfection, acpxRAdeletion strain was generated and found to have a colonization defect during infection. This defect was independent of an altered growth rate or a defective type III secretion system, and single-copy chromosomal complementation ofcpxRArestored virulence. TheC. rodentiumstrains were then tested in C3H/HeJ mice, a lethal intestinal infection model. Mice infected with the ΔcpxRAstrain survived infection, whereas mice infected with the wild-type or complemented strains succumbed to infection. Furthermore, we found that thecpxRAexpression level was higher during early infection than at a later time point. Taken together, these data demonstrate that the CpxRA two-component signal transduction system is essential for thein vivovirulence ofC. rodentium. In addition, these data suggest that fine-tunedcpxRAexpression is important for infection. This is the first study that identifies aC. rodentiumtwo-component transduction system required for pathogenesis. This study further indicates that CpxRA is an interesting target for therapeutics against enteric pathogens.

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rgf Encodes a Novel Two-Component Signal Transduction System of Streptococcus agalactiae

Infection and Immunity ◽

10.1128/iai.70.5.2434-2440.2002 ◽

2002 ◽

Vol 70 (5) ◽

pp. 2434-2440 ◽

Cited By ~ 46

Author(s):

Barbara Spellerberg ◽

Eva Rozdzinski ◽

Simone Martin ◽

Josefine Weber-Heynemann ◽

Rudolf Lütticken

Keyword(s):

Signal Transduction ◽

Amino Acids ◽

Histidine Kinase ◽

Wild Type ◽

Signal Transduction System ◽

Transcription Analysis ◽

Ecm Proteins ◽

Fibrinogen Binding ◽

Two Component ◽

Two Component Signal Transduction

ABSTRACT The adhesion of gram-positive bacteria to extracellular matrix (ECM) proteins is regarded as an important determinant of pathogenicity. A comparison of the adhesion of Streptococcus agalactiae strain O90R to different ECM proteins showed that the most pronounced binding could be observed for immobilized fibrinogen. To investigate the genetic determinants of S. agalactiae fibrinogen binding, a pGhost9:ISS1 mutant library was screened for mutants displaying reduced agglutination of fibrinogen-coated latex beads. A putative two-component signal transduction system was identified and designated rgfBDAC. It comprises genes encoding a putative response regulator of 218 amino acids and a putative histidine kinase of 426 amino acids. Comparison of the deduced proteins with the GenBank database revealed a significant similarity to quorum-sensing systems of gram-positive pathogens. Transcription analysis of the rgf locus showed that the encoding genes are located on one transcript. To further characterize the influence of the putative histidine kinase encoded in the rgf locus on the adhesion of S. agalactiae to immobilized fibrinogen, a targeted mutant of rgfC was generated. In comparison to the wild-type strain this mutant demonstrated altered fibrinogen binding capacities depending on bacterial cell density. Transcription analysis of secreted and surface-localized S. agalactiae proteins in the wild type and the rgfC mutant strain revealed that mRNA levels of the C5a peptidase gene scpB were increased in the mutant strain while the transcription of the secreted CAMP factor gene cfb was unaffected by this mutation. Based on these results, we hypothesize that rgf regulates the expression of bacterial cell surface components.

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Two-Component Signal Transduction System SaeRS Positively RegulatesStaphylococcus epidermidisGlucose Metabolism

The Scientific World JOURNAL ◽

10.1155/2014/908121 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Qiang Lou ◽

Yijun Qi ◽

Yuanfang Ma ◽

Di Qu

Keyword(s):

Signal Transduction ◽

Staphylococcus Epidermidis ◽

Gel Electrophoresis ◽

Laser Desorption ◽

Tca Cycle ◽

Wild Type ◽

Signal Transduction System ◽

Two Dimensional Gel Electrophoresis ◽

Two Component ◽

Two Component Signal Transduction

Staphylococcus epidermidis, which is a causative pathogen of nosocomial infection, expresses its virulent traits such as biofilm and autolysis regulated by two-component signal transduction system SaeRS. In this study, we performed a proteomic analysis of differences in expression between theS. epidermidis1457 wild-type andsaeRSmutant to identify candidates regulated by saeRS using two-dimensional gel electrophoresis (2-DE) combined with matrix-assisted laser desorption/lonization mass spectrometry (MALDI-TOF-MS). Of 55 identified proteins that significantly differed in expression between the two strains, 15 were upregulated and 40 were downregulated. The downregulated proteins included enzymes related to glycolysis and TCA cycle, suggesting that glucose is not properly utilized inS. epidermidiswhensaeRSwas deleted. The study will be helpful for treatment ofS. epidermidisinfection from the viewpoint of metabolic modulation dependent on two-component signal transduction system SaeRS.

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