The <i>Burkholderia cenocepacia</i> sensor kinase hybrid AtsR is a global regulator modulating quorum‐sensing signalling

Aubert, Daniel; O'Grady, Eoin P.; Hamad, Mohamad A.; Sokol, Pamela A.; Valvano, Miguel A.

doi:10.1111/j.1462-2920.2012.02828.x

Cited by 31 publications

(36 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S1 in the supplemental material). The AtsR protein from B. cenocepacia is 56.9% identical at the amino acid level and was found to mediate bacterial attachment to abiotic and biotic surfaces and host-pathogen interactions in that opportunistic pathogen (37,38).…”

Section: Identification Of Eepr and Eepsmentioning

confidence: 99%

Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites

et al. 2015

View full text Add to dashboard Cite

Serratia marcescens generates secondary metabolites and secreted enzymes, and it causes hospital infections and communityacquired ocular infections. Previous studies identified cyclic AMP (cAMP) receptor protein (CRP) as an indirect inhibitor of antimicrobial secondary metabolites. Here, we identified a putative two-component regulator that suppressed crp mutant phenotypes. Evidence supports that the putative response regulator eepR was directly transcriptionally inhibited by cAMP-CRP. EepR and the putative sensor kinase EepS were necessary for the biosynthesis of secondary metabolites, including prodigiosin-and serratamolide-dependent phenotypes, swarming motility, and hemolysis. Recombinant EepR bound to the prodigiosin and serratamolide promoters in vitro. Together, these data introduce a novel regulator of secondary metabolites that directly connects the broadly conserved metabolism regulator CRP with biosynthetic genes that may contribute to competition with other microbes. IMPORTANCEThis study identifies a new transcription factor that is directly controlled by a broadly conserved transcription factor, CRP. CRP is well studied in its role to help bacteria respond to the amount of nutrients in their environment. The new transcription factor EepR is essential for the bacterium Serratia marcescens to produce two biologically active compounds, prodigiosin and serratamolide. These two compounds are antimicrobial and may allow S. marcescens to compete for limited nutrients with other microorganisms. Results from this study tie together the CRP environmental nutrient sensor with a new regulator of antimicrobial compounds. Beyond microbial ecology, prodigiosin and serratamolide have therapeutic potential; therefore, understanding their regulation is important for both applied and basic science. In order for organisms to survive and prosper, they must be able to sense their environment and effectively compete with other organisms. To respond to these environmental changes, bacteria have developed elaborate transcriptional regulatory systems that enable fine-tuning of factors that allow for their adaptation and proliferation. One of the most studied signaling systems involved in adaptation to the nutritive status of the environment is the cyclic AMP (cAMP)-associated catabolite repression system (1-4). The second messenger cAMP has been classified as an alarmone that induces positive regulation of alternative carbon transport systems in times of carbon/fuel deprivation (5). In addition to catabolite repression control, this system also can positively regulate flagellum production in unfavorable conditions (6) and activate attachment factors in nutrient-rich conditions (7).Evidence suggests that cAMP-cAMP receptor protein (CRP) can directly bind to and promote expression of secondary metabolite genes involved in antibiotic production in Streptomyces coelicolor (2). A positive or negative role for cAMP has been suggested for control of antimicrobial production in other organisms, including fungi, although dire...

show abstract

Section: Identification Of Eepr and Eepsmentioning

confidence: 99%

Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites

et al. 2015

View full text Add to dashboard Cite

show abstract

“…This bacterium is also virulent in zebrafish (11), alfalfa, nematodes, and insect infection models (12) and can survive within amoebae and macrophages (13,14). We have previously identified AtsR (Adhesion and type six secretion system Regulator), which negatively regulates the expression of quorum sensing-regulated virulence factors in B. cenocepacia (15,16). B. cenocepacia strains have two N-acylhomoserine lactone-dependent quorum-sensing systems, CepIR and CciIR, that coordinate the expression of ZmpA and ZmpB zinc metalloproteases and other virulence factors during infection (17)(18)(19)(20)(21).…”

mentioning

confidence: 99%

“…B. cenocepacia strains have two N-acylhomoserine lactone-dependent quorum-sensing systems, CepIR and CciIR, that coordinate the expression of ZmpA and ZmpB zinc metalloproteases and other virulence factors during infection (17)(18)(19)(20)(21). In the absence of atsR, expression of cepIR and cciIR is up-regulated and mediates early and increased N-acylhomoserine lactone production, suggesting that AtsR plays a role in controlling virulence gene expression by modulating the timing of quorum sensing signaling (16). AtsR also represses the expression of virulence genes by an N-acylhomoserine lactoneindependent mechanism (16).…”

mentioning

confidence: 99%

“…In the absence of atsR, expression of cepIR and cciIR is up-regulated and mediates early and increased N-acylhomoserine lactone production, suggesting that AtsR plays a role in controlling virulence gene expression by modulating the timing of quorum sensing signaling (16). AtsR also represses the expression of virulence genes by an N-acylhomoserine lactoneindependent mechanism (16). Consequently, inactivation of atsR in B. cenocepacia also leads to increased biofilm formation, adherence to polystyrene and lung epithelial cells, extracellular protease secretion, and expression of a type 6 secretion system (T6SS).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of the AtsR Hybrid Sensor Kinase Phosphorelay Pathway and Identification of Its Response Regulator in Burkholderia cenocepacia

Khodai-Kalaki

Aubert

Valvano

2013

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: AtsR is a Burkholderia cenocepacia hybrid sensor kinase that negatively regulates quorum sensing. Results: The AtsR phosphorelay mechanism includes the AtsT cognate response regulator. Conclusion: AtsR regulation occurs through phosphorylation of AtsT, which is fine-tuned by the AtsR receiver domain. Significance: The AtsR/AtsT phosphorelay pathway uncovers a major global regulator of B. cenocepacia pathogenicity.

show abstract

“…Bacterial kinases participate in the regulation of cellular processes known to be important for biofilm formation, such as quorum sensing (17,18) and production of extracellular matrix components (19,20). In recent years, kinases have been assigned a high priority as candidate drug targets due to their endogenous smallmolecule-binding motifs and their importance in cellular functions (21).…”

mentioning

confidence: 99%

Inhibition of Salmonella enterica Biofilm Formation Using Small-Molecule Adenosine Mimetics

Koopman

Marshall

Bhatiya

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

cBiofilms have been widely implicated in chronic infections and environmental persistence of Salmonella enterica, facilitating enhanced colonization of surfaces and increasing the ability of the bacteria to be transmitted to new hosts. Salmonella enterica serovar Typhi biofilm formation on gallstones from humans and mice enhances gallbladder colonization and bacterial shedding, while Salmonella enterica serovar Typhimurium biofilms facilitate long-term persistence in a number of environments important to food, medical, and farming industries. Salmonella regulates expression of many virulence-and biofilm-related processes using kinase-driven pathways. Kinases play pivotal roles in phosphorylation and energy transfer in cellular processes and possess an ATP-binding pocket required for their functions. Many other cellular proteins also require ATP for their activity. Here we test the hypothesis that pharmacological interference with ATP-requiring enzymes utilizing adenosine mimetic compounds would decrease or inhibit bacterial biofilm formation. Through the screening of a 3,000-member ATP mimetic library, we identified a single compound (compound 7955004) capable of significantly reducing biofilm formation by S. Typhimurium and S. Typhi. The compound was not bactericidal or bacteriostatic toward S. Typhimurium or cytotoxic to mammalian cells. An ATPSepharose affinity matrix technique was used to discover potential protein-binding targets of the compound and identified GroEL and DeoD. Compound 7955004 was screened against other known biofilm-forming bacterial species and was found to potently inhibit biofilms of Acinetobacter baumannii as well. The identification of a lead compound with biofilm-inhibiting capabilities toward Salmonella provides a potential new avenue of therapeutic intervention against Salmonella biofilm formation, with applicability to biofilms of other bacterial pathogens.

show abstract

The Burkholderia cenocepacia sensor kinase hybrid AtsR is a global regulator modulating quorum‐sensing signalling

Cited by 31 publications

References 55 publications

Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites

Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites

Characterization of the AtsR Hybrid Sensor Kinase Phosphorelay Pathway and Identification of Its Response Regulator in Burkholderia cenocepacia

Inhibition of Salmonella enterica Biofilm Formation Using Small-Molecule Adenosine Mimetics

Contact Info

Product

Resources

About