scholarly journals Role of Two-Component System Response Regulator bceR in the Antimicrobial Resistance, Virulence, Biofilm Formation, and Stress Response of Group B Streptococcus

2019 ◽  
Vol 10 ◽  
Author(s):  
Ying Yang ◽  
Mingjing Luo ◽  
Haokui Zhou ◽  
Carmen Li ◽  
Alison Luk ◽  
...  
2005 ◽  
Vol 187 (3) ◽  
pp. 1105-1113 ◽  
Author(s):  
Sheng-Mei Jiang ◽  
Michael J. Cieslewicz ◽  
Dennis L. Kasper ◽  
Michael R. Wessels

ABSTRACT Group B Streptococcus (GBS) is frequently carried in the gastrointestinal or genitourinary tract as a commensal organism, yet it has the potential to cause life-threatening infection in newborn infants, pregnant women, and individuals with chronic illness. Regulation of virulence factor expression may affect whether GBS behaves as an asymptomatic colonizer or an invasive pathogen, but little is known about how such factors are controlled in GBS. We now report the characterization of a GBS locus that encodes a two-component regulatory system similar to CsrRS (or CovRS) in Streptococcus pyogenes. Inactivation of csrR, encoding the putative response regulator, in two unrelated wild-type strains of GBS resulted in a marked increase in production of beta-hemolysin/cytolysin and a striking decrease in production of CAMP factor, an unrelated cytolytic toxin. Quantitative RNA hybridization experiments revealed that these two phenotypes were associated with a marked increase and decrease in expression of the corresponding genes, cylE and cfb, respectively. The CsrR mutant strains also displayed increased expression of scpB encoding C5a peptidase. Similar, but less marked, changes in gene expression were observed in CsrS (putative sensor component) mutants, evidence that CsrR and CsrS constitute a functional two-component system. Experimental infection studies in mice demonstrated reduced virulence of both CsrR and CsrS mutant strains relative to the wild type. Together, these results indicate that CsrRS regulates expression of multiple GBS virulence determinants and is likely to play an important role in GBS pathogenesis.


PLoS ONE ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. e14658 ◽  
Author(s):  
Rim Al Safadi ◽  
Laurent Mereghetti ◽  
Mazen Salloum ◽  
Marie-Frédérique Lartigue ◽  
Isabelle Virlogeux-Payant ◽  
...  

2007 ◽  
Vol 189 (17) ◽  
pp. 6293-6302 ◽  
Author(s):  
Sang-Joon Ahn ◽  
Robert A. Burne

ABSTRACT The Streptococcus mutans atlA gene encodes an autolysin required for biofilm maturation and biogenesis of a normal cell surface. We found that the capacity to form biofilms by S. mutans, one of the principal causative agents of dental caries, was dramatically impaired by growth of the organism in an aerated environment and that cells exposed to oxygen displayed marked changes in surface protein profiles. Inactivation of the atlA gene alleviated repression of biofilm formation in the presence of oxygen. Also, the formation of long chains, a characteristic of AtlA-deficient strains, was less evident in cells grown with aeration. The SMu0629 gene is immediately upstream of atlA and encodes a product that contains a C-X-X-C motif, a characteristic of thiol-disulfide oxidoreductases. Inactivation of SMu0629 significantly reduced the levels of AtlA protein and led to resistance to autolysis. The SMu0629 mutant also displayed an enhanced capacity to form biofilms in the presence of oxygen compared to that of the parental strain. The expression of SMu0629 was shown to be under the control of the VicRK two-component system, which influences oxidative stress tolerance in S. mutans. Disruption of vicK also led to inhibition of processing of AtlA, and the mutant was hyperresistant to autolysis. When grown under aerobic conditions, the vicK mutant also showed significantly increased biofilm formation compared to strain UA159. This study illustrates the central role of AtlA and VicK in orchestrating growth on surfaces and envelope biogenesis in response to redox conditions.


Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1043-1051 ◽  
Author(s):  
Guillaume Cottarel

The Schizosaccharomyces pombe cdc2-3w weel-50 double mutant displays a temperature-sensitive lethal phenotype termed mitotic catastrophe. Six mitotic catastrophe suppressor (mcs1-6) genes were identified in a genetic screen designed to identify regulators of cdc2. Mutations in mcs1-6 suppress the cdc2-3w weel-50 temperature-sensitive growth defect. Here, the cloning of mcs4 is described. The mcs4 gene product displays significant sequence homology to members of the two-component system response regulator protein family. Strains carrying the mcs4 and cdc25 mutations display a synthetic osmotic lethal phenotype along with an inability to grow on minimal synthetic medium. These phenotypes are suppressed by a mutation in wee1. In addition, the wis1 gene, encoding a stress-activated mitogen-activated protein kinase kinase, was identified as a dosage suppressor in this screen. These findings link the two-component signal transduction system to stress response and cell cycle control in S. pombe.


2010 ◽  
pp. 108-117
Author(s):  
Md Manjurul Haque ◽  
Shinji Tsuyumu

To elucidate the role of PhoP-PhoQ two-component system in biofilm formation by the phytopathogen Dickeya dadantii (formerly Erwinia chrysanthemi) strain 3937, we used marker-exchanged mutants deficient in both phoP and phoQ. A biofilm-inducing medium, salt-optimized broth plus glycerol (SOBG) which contains salt-optimized broth (SOB) plus 2% of glycerol, supported biofilm formation by D. dadantii strain 3937 to a greater extent than either M63 glycerol minimal medium or yeast extract peptone (YP) medium or Luria-Bertani (LB) medium. In addition, magnesium greatly induced biofilm formation. It was found that both the phoP and phoQ mutants exhibited enhanced ability to form a biofilm on the surface of the glass test tube as compared to the wild-type strain in SOBG medium containing high concentration of magnesium. In addition, under high magnesium condition, both the mutants produced elevated level of exopolysaccharide. Accordingly, genes responsible for exopolysaccharide production (weaP, wza and wzc) were derepressed in the mutants. These results suggest that the PhoP-PhoQ two-component system may regulate formation of biofilm, at least in part, by transcriptional control of genes responsible for exopolysaccharide biosynthesis of D. dadantii strain 3937. Since biofilm-associated bacteria showed more tolerance to acidic pH and high osmotic stress, it is apparent that the formation of biofilm may be an important factor for the survival of D. dadantii strain 3937 in unfavorable environment.


2018 ◽  
Author(s):  
Ying Yang ◽  
Mingjing Luo ◽  
Haokui ◽  
Carmen Li ◽  
Alison W. S. Luk ◽  
...  

AbstractThe hypervirulent Group B Streptococcus (Streptococcus agalactiae, GBS) serogroup III clonal cluster 17 has been associated with neonatal GBS invasive disease and meningits. Serogroup III, ST283 has recently been implicated in invasive disease among non-pregnant adults in Asia. These strains cluster with strains from freshwater fishes from aquaculture and a foodborne outbreak of sepsis, especially with septic arthritis, had been linked to such consumption in Singapore in 2015. Through comparative genome analyses of invasive and non-invasive strains of ST283, we identified a truncated response regulator gene in the non-invasive strain. This two component response gene, previously named a DNA binding regulator, is conserved among GBS strains and is a homologue ofBacillus subtilis BceR, the response regulator of the BceRSAB system. Loss of function of theBceRresponse gene in the invasive GBS strain demonstrated bacitracin susceptibility inΔBceRmutant with MICs of 256-fold and four-fold reduction in bacitracin and human cathelicin LL-37 compared to wild type and complementation strains. Upregulation ofdltAof wild type strain vsΔBceRmutant was demonstrated (p<0.0001), and was previously shown inStaphylococcus aureusto resist and repel cationic peptides through excess positive charges with D-alanylation of teichoic acids on the cell wall. In addition,ΔBceRmutant was less susceptible under oxidative stress under H2O2stress when compared to wild type strain (p<0.001) and inhibited biofilm formation (p<0.05 andp< 0.0001 for crystal violet staining and cfu counts). TheΔBceRmutant also showed reduced mortality as compared to wild type strain (p<0.01) in a murine infection model. Taken together,BceRSis involved in bacitracin and antimicrobial peptide resistance, survival under oxidative stress, biofilm formation and play an important role in the virulence of GBS.Author SummaryTwo-component systems (TCSs) play an important role in virulence in bacteria, and are involved in detecting environmental changes. AlthoughS. agalactiaewas reported to contain more predicted TCSs thanStreptococcus pneumoniae,few have been studied in detail. In this work, comparative genomic analysis of GBS invasive (hyper-virulent) and non-invasive serotype III-4 strains were performed to determine any gene differences that may account for severity of disease in humans.BceR-likeTCS was selected and suspected to be involved in virulence, and thusBceRwas deleted in a hyper-virulent GBS serotype III-4 strain. We demonstrated that thisBceR-likeTCS is involved in GBS virulence and induced proinflammatory host immune responses. Our study of TCSBceRmay guide further research into the role of other TCSs in GBS pathogenicity, and further explore therapeutic targets for GBS disease.


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