scholarly journals ScmR, a global regulator of gene expression, quorum sensing, pH homeostasis, and virulence in Burkholderia thailandensis

2019 ◽  
Author(s):  
Servane Le Guillouzer ◽  
Marie-Christine Groleau ◽  
Florian Mauffrey ◽  
Eric Déziel
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Burkholderia Pseudomallei ◽  
Transcriptional Regulator ◽  
Central Component ◽  
Human Pathogens ◽  
Global Regulator ◽  
Ph Homeostasis ◽  
Burkholderia Thailandensis ◽  
Wide Range

AbstractThe nonpathogenic soil saprophyte Burkholderia thailandensis is a member of the Burkholderia pseudomallei-thailandensis-mallei (Bptm) group, which also comprises the closely related human pathogens Burkholderia pseudomallei and Burkholderia mallei responsible for the diseases melioidosis and glanders, respectively. ScmR, a recently identified LysR-type transcriptional regulator (LTTR) in B. thailandensis acts as a global transcriptional regulator throughout the stationary phase, and modulates the production of a wide range of secondary metabolites, including N-acyl-L-homoserine lactones (AHLs) and 4-hydroxy-3-methyl-2-alkylquinoline (HMAQ), virulence in the model host Caenorhabditis elegans, as well as several quorum sensing (QS)-dependent phenotypes. We have investigated the role of ScmR in B. thailandensis strain E264 during the exponential phase. We used RNA-Sequencing (RNA-Seq) transcriptomic analyses to identify the ScmR regulon, which was compared to the QS-controlled regulon, showing a considerable overlap between the ScmR-regulated genes and those controlled by QS. We characterized several genes modulated by ScmR, using quantitative reverse transcription-PCR (qRT-PCR) or mini-CTX-lux transcriptional reporters, including the oxalate biosynthetic gene obc1 required for pH homeostasis, the orphan LuxR-type transcriptional regulator BtaR5-encoding gene, the bsa (Burkholderia secretion apparatus) type III secretion system (T3SS) genes essential for both B. pseudomallei and B. mallei pathogenicity, as well as the scmR gene itself. We confirmed that the transcription of scmR is under QS control, presumably ensuring fine-tuned modulation of gene expression. Finally, we demonstrate that ScmR influences virulence using the fruit fly model host Drosophila melanogaster. We conclude that ScmR represents a central component of the B. thailandensis QS regulatory network.ImportanceCoordination of the expression of genes associated with bacterial virulence and environmental adaptation is often dependent on quorum sensing (QS). The QS circuitry of the nonpathogenic bacterium Burkholderia thailandensis, which is widely used as a model system for the study of the human pathogen Burkholderia pseudomallei, is complex. We found that the recently identified LysR-type transcriptional regulator (LTTR), ScmR, which is highly conserved and involved in the control of virulence/survival factors in the Burkholderia genus, is a global regulator mediating gene expression through the multiple QS systems coexisting in B. thailandensis, as well as independently of QS. We conclude that ScmR represents a key QS modulatory network element, ensuring tight regulation of the transcription of QS-controlled genes, particularly those required for acclimatization to the environment.

scholarly journals ScmR, a Global Regulator of Gene Expression, Quorum Sensing, pH Homeostasis, and Virulence in Burkholderia thailandensis

2020 ◽  
Vol 202 (13) ◽  
Author(s):  
Servane Le Guillouzer ◽  
Marie-Christine Groleau ◽  
Florian Mauffrey ◽  
Eric Déziel
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Burkholderia Pseudomallei ◽  
Transcriptional Regulator ◽  
Central Component ◽  
Global Regulator ◽  
Ph Homeostasis ◽  
Burkholderia Thailandensis ◽  
Content Type ◽  
Wide Range

ABSTRACT The nonpathogenic soil saprophyte Burkholderia thailandensis is a member of the Burkholderia pseudomallei/B. thailandensis/B. mallei group, which also comprises the closely related human pathogens B. pseudomallei and Burkholderia mallei responsible for the melioidosis and glanders diseases, respectively. ScmR, a recently identified LysR-type transcriptional regulator in B. thailandensis, acts as a global transcriptional regulator throughout the stationary phase and modulates the production of a wide range of secondary metabolites, including N-acyl-l-homoserine lactones and 4-hydroxy-3-methyl-2-alkylquinolines and virulence in the Caenorhabditis elegans nematode worm host model, as well as several quorum sensing (QS)-dependent phenotypes. We have investigated the role of ScmR in B. thailandensis strain E264 during the exponential phase. We used RNA sequencing transcriptomic analyses to identify the ScmR regulon, which was compared to the QS-controlled regulon, showing a considerable overlap between the ScmR-regulated genes and those controlled by QS. We characterized several genes modulated by ScmR using quantitative reverse transcription-PCR or mini-CTX-lux transcriptional reporters, including the oxalate biosynthetic gene obc1 required for pH homeostasis, the orphan LuxR-type transcriptional regulator BtaR5-encoding gene, and the bsa (Burkholderia secretion apparatus) type III secretion system genes essential for both B. pseudomallei and B. mallei pathogenicity, as well as the scmR gene itself. We confirmed that the transcription of scmR is under QS control, presumably ensuring fine-tuned modulation of gene expression. Finally, we demonstrated that ScmR influences virulence using the fruit fly model host Drosophila melanogaster. We conclude that ScmR represents a central component of the B. thailandensis QS regulatory network. IMPORTANCE Coordination of the expression of genes associated with bacterial virulence and environmental adaptation is often dependent on quorum sensing (QS). The QS circuitry of the nonpathogenic bacterium Burkholderia thailandensis, widely used as a model system for the study of the human pathogen Burkholderia pseudomallei, is complex. We found that the LysR-type transcriptional regulator, ScmR, which is highly conserved and involved in the control of virulence/survival factors in the Burkholderia genus, is a global regulator mediating gene expression through the multiple QS systems coexisting in B. thailandensis, as well as QS independently. We conclude that ScmR represents a key QS modulatory network element, ensuring tight regulation of the transcription of QS-controlled genes, particularly those required for acclimatization to the environment.

scholarly journals The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in Yersinia pestis during Planktonic Growth and Growth in Biofilms

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Jeremy T. Ritzert ◽  
George Minasov ◽  
Ryan Embry ◽  
Matthew J. Schipma ◽  
Karla J. F. Satchell
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Carbon Source ◽  
Cyclic Amp ◽  
Yersinia Pestis ◽  
Carbon Sources ◽  
Transcriptional Regulator ◽  
Receptor Protein ◽  
Content Type ◽  
Bacterial Physiology

ABSTRACT Cyclic AMP (cAMP) receptor protein (Crp) is an important transcriptional regulator of Yersinia pestis. Expression of crp increases during pneumonic plague as the pathogen depletes glucose and forms large biofilms within lungs. To better understand control of Y. pestis Crp, we determined a 1.8-Å crystal structure of the protein-cAMP complex. We found that compared to Escherichia coli Crp, C helix amino acid substitutions in Y. pestis Crp did not impact the cAMP dependency of Crp to bind DNA promoters. To investigate Y. pestis Crp-regulated genes during plague pneumonia, we performed RNA sequencing on both wild-type and Δcrp mutant bacteria growing in planktonic and biofilm states in minimal media with glucose or glycerol. Y. pestis Crp was found to dramatically alter expression of hundreds of genes in a manner dependent upon carbon source and growth state. Gel shift assays confirmed direct regulation of the malT and ptsG promoters, and Crp was then linked to Y. pestis growth on maltose as a sole carbon source. Iron regulation genes ybtA and fyuA were found to be indirectly regulated by Crp. A new connection between carbon source and quorum sensing was revealed as Crp was found to regulate production of acyl-homoserine lactones (AHLs) through direct and indirect regulation of genes for AHL synthetases and receptors. AHLs were subsequently identified in the lungs of Y. pestis-infected mice when crp expression was highest in Y. pestis biofilms. Thus, in addition to the well-studied pla gene, other Crp-regulated genes likely have important functions during plague infection. IMPORTANCE Bacterial pathogens have evolved extensive signaling pathways to translate environmental signals into changes in gene expression. While Crp has long been appreciated for its role in regulating metabolism of carbon sources in many bacterial species, transcriptional profiling has revealed that this protein regulates many other aspects of bacterial physiology. The plague pathogen Y. pestis requires this global regulator to survive in blood, skin, and lungs. During disease progression, this organism adapts to changes within these niches. In addition to regulating genes for metabolism of nonglucose sugars, we found that Crp regulates genes for virulence, metal acquisition, and quorum sensing by direct or indirect mechanisms. Thus, this single transcriptional regulator, which responds to changes in available carbon sources, can regulate multiple critical behaviors for causing disease.

scholarly journals Malleilactone Is a Burkholderia pseudomallei Virulence Factor Regulated by Antibiotics and Quorum Sensing

2018 ◽  
Vol 200 (14) ◽  
Author(s):  
Jennifer R. Klaus ◽  
Jacqueline Deay ◽  
Benjamin Neuenswander ◽  
Wyatt Hursh ◽  
Zhe Gao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Quorum Sensing ◽  
Virulence Factor ◽  
Mammalian Cells ◽  
Burkholderia Pseudomallei ◽  
Gene Clusters ◽  
Close Relative ◽  
Burkholderia Thailandensis ◽  
Content Type

ABSTRACT Burkholderia pseudomallei , the causative agent of melioidosis, encodes almost a dozen predicted polyketide (PK) biosynthetic gene clusters. Many of these are regulated by LuxR-I-type acyl-homoserine (AHL) quorum-sensing systems. One of the PK gene clusters, the mal gene cluster, is conserved in the close relative Burkholderia thailandensis . The B. thailandensis mal genes code for the cytotoxin malleilactone and are regulated by a genetically linked LuxR-type transcription factor, MalR. Although AHLs typically interact with LuxR-type proteins to modulate gene transcription, the B. thailandensis MalR does not appear to be an AHL receptor. Here, we characterize the mal genes and MalR in B. pseudomallei . We use chemical analyses to demonstrate that the B. pseudomallei mal genes code for malleilactone. Our results show that MalR and the mal genes contribute to the ability of B. pseudomallei to kill Caenorhabditis elegans . In B. thailandensis , antibiotics like trimethoprim can activate MalR by driving transcription of the mal genes, and we demonstrate that some of the same antibiotics induce expression of B. pseudomallei malR . We also demonstrate that B. pseudomallei MalR does not respond directly to AHLs. Our results suggest that MalR is indirectly repressed by AHLs, possibly through a repressor, ScmR. We further show that malleilactone is a B. pseudomallei virulence factor and provide the foundation for understanding how malleilactone contributes to the pathology of melioidosis infections. IMPORTANCE Many bacterially produced polyketides are cytotoxic to mammalian cells and are potentially important contributors to pathogenesis during infection. We are interested in the polyketide gene clusters present in Burkholderia pseudomallei , which causes the often-fatal human disease melioidosis. Using knowledge gained by studies in the close relative Burkholderia thailandensis , we show that one of the B. pseudomallei polyketide biosynthetic clusters produces a cytotoxic polyketide, malleilactone. Malleilactone contributes to B. pseudomallei virulence in a Caenorhabditis elegans infection model and is regulated by an orphan LuxR family quorum-sensing transcription factor, MalR. Our studies demonstrate that malleilactone biosynthesis or MalR could be new targets for developing therapeutics to treat melioidosis.

scholarly journals Synthetic Riboswitches That Induce Gene Expression in Diverse Bacterial Species

2010 ◽  
Vol 76 (23) ◽  
pp. 7881-7884 ◽  
Author(s):  
Shana Topp ◽  
Colleen M. K. Reynoso ◽  
Jessica C. Seeliger ◽  
Ian S. Goldlust ◽  
Shawn K. Desai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacterial Species ◽  
Human Pathogens ◽  
Expression Systems ◽  
Genetic Studies ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Control Gene Expression ◽  
Diverse Species ◽  
Wide Range

ABSTRACT We developed a series of ligand-inducible riboswitches that control gene expression in diverse species of Gram-negative and Gram-positive bacteria, including human pathogens that have few or no previously reported inducible expression systems. We anticipate that these riboswitches will be useful tools for genetic studies in a wide range of bacteria.

scholarly journals In VivoProgrammed Gene Expression Based on Artificial Quorum Networks

2015 ◽  
Vol 81 (15) ◽  
pp. 4984-4992 ◽  
Author(s):  
Teng Chu ◽  
Yajun Huang ◽  
Mingyu Hou ◽  
Qiyao Wang ◽  
Jingfan Xiao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Cell Density ◽  
Protective Antigen ◽  
Expression System ◽  
Edwardsiella Tarda ◽  
Content Type ◽  
Genetic Components ◽  
Wide Range

ABSTRACTThe quorum sensing (QS) system, as a well-functioning population-dependent gene switch, has been widely applied in many gene circuits in synthetic biology. In our work, an efficient cell density-controlled expression system (QS) was established via engineering of theVibrio fischeri luxI-luxRquorum sensing system. In order to achievein vivoprogrammed gene expression, a synthetic binary regulation circuit (araQS) was constructed by assembling multiple genetic components, including the quorum quenching protein AiiA and the arabinose promoter ParaBAD, into the QS system.In vitroexpression assays verified that the araQS system was initiated only in the absence of arabinose in the medium at a high cell density.In vivoexpression assays confirmed that the araQS system presented anin vivo-triggered and cell density-dependent expression pattern. Furthermore, the araQS system was demonstrated to function well in different bacteria, indicating a wide range of bacterial hosts for use. To explore its potential applicationsin vivo, the araQS system was used to control the production of a heterologous protective antigen in an attenuatedEdwardsiella tardastrain, which successfully evoked efficient immune protection in a fish model. This work suggested that the araQS system could program bacterial expressionin vivoand might have potential uses, including, but not limited to, bacterial vector vaccines.

scholarly journals A LysR family transcriptional regulator modulates biofilm formation and protease production in Burkholderia cenocepacia

2021 ◽  
Author(s):  
Kai Wang ◽  
Xia Li ◽  
Chunxi Yang ◽  
Shihao Song ◽  
Chaoyu Cui ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Target Gene ◽  
Transcriptional Regulator ◽  
Signaling Network ◽  
Burkholderia Cenocepacia ◽  
Protease Production ◽  
Biological Functions ◽  
Lysr Family

Quorum sensing (QS) signals are widely employed by bacteria to regulate biological functions in response to cell densities. Previous studies showed that Burkholderia cenocepacia mostly utilizes two types of QS systems, including the N-acylhomoserine lactone (AHL) and cis-2-dodecenoic acid (BDSF) systems, to regulate biological functions. We demonstrated here that a LysR family transcriptional regulator Bcal3178 controls the QS-regulated phenotypes, including biofilm formation and protease production, in B. cenocepacia H111. Expression of Bcal3178 at transcriptional level was obviously down-regulated in both the AHL-deficient and BDSF-deficient mutant strains comparing to the wild-type H111 strain. It was further identified that Bcal3178 regulated target gene expression by directly binding to the promoter DNA regions. We also revealed that Bcal3178 was directly controlled by the AHL system regulator CepR. These results show that Bcal3178 is a new downstream component of the QS signaling network that modulates a subset of genes and functions co-regulated by the AHL and BDSF QS systems in B. cenocepacia. IMPORTANCE Burkholderia cenocepacia is an important opportunistic pathogen in humans, which utilizes the BDSF and AHL quorum sensing (QS) systems to regulate biological functions and virulence. We demonstrated here that a new downstream regulator Bcal3178 of the QS signaling network controls biofilm formation and protease production. Bcal3178 is a LysR family transcriptional regulator modulated by both the BDSF and AHL QS systems. Furthermore, Bcal3178 controls many target genes which are regulated by the QS systems in B. cenocepacia. Collectively, our findings depict a novel molecular mechanism with which QS systems regulate some target gene expression and biological functions by modulating the expression level of a LysR family transcriptional regulator in B. cenocepacia.

scholarly journals A structural perspective on the mechanisms of quorum sensing activation in bacteria

2015 ◽  
Vol 87 (4) ◽  
pp. 2189-2203 ◽  
Author(s):  
CAROLINA LIXA ◽  
AMANDA MUJO ◽  
CRISTIANE D. ANOBOM ◽  
ANDERSON S. PINHEIRO
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Rational Design ◽  
Three Dimensional ◽  
Cell Communication ◽  
Dependent Manner ◽  
Regulate Gene Expression ◽  
Wide Range ◽  
A Cell ◽  
Regulate Gene

Bacteria are able to synchronize the population behavior in order to regulate gene expression through a cell-to-cell communication mechanism called quorum sensing. This phenomenon involves the production, detection and the response to extracellular signaling molecules named autoinducers, which directly or indirectly regulate gene expression in a cell density-dependent manner. Quorum sensing may control a wide range of biological processes in bacteria, such as bioluminescence, virulence factor production, biofilm formation and antibiotic resistance. The autoinducers are recognized by specific receptors that can either be membrane-bound histidine kinase receptors, which work by activating cognate cytoplasmic response regulators, or cytoplasmic receptors acting as transcription factors. In this review, we focused on the cytosolic quorum sensing regulators whose three-dimensional structures helped elucidate their mechanisms of action. Structural studies of quorum sensing receptors may enable the rational design of inhibitor molecules. Ultimately, this approach may represent an effective alternative to treat infections where classical antimicrobial therapy fails to overcome the microorganism virulence.

scholarly journals Cross-Species Comparison of the Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei Quorum-Sensing Regulons

2014 ◽  
Vol 196 (22) ◽  
pp. 3862-3871 ◽  
Author(s):  
C. D. Majerczyk ◽  
M. J. Brittnacher ◽  
M. A. Jacobs ◽  
C. D. Armour ◽  
M. C. Radey ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Burkholderia Pseudomallei ◽  
Burkholderia Mallei ◽  
Species Comparison ◽  
Burkholderia Thailandensis ◽  
Cross Species Comparison

scholarly journals RsaL provides quorum sensing homeostasis and functions as a global regulator of gene expression in Pseudomonas aeruginosa

2007 ◽  
Vol 66 (6) ◽  
pp. 1557-1565 ◽  
Author(s):  
Giordano Rampioni ◽  
Martin Schuster ◽  
Everett Peter Greenberg ◽  
Iris Bertani ◽  
Marco Grasso ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Global Regulator
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