scholarly journals Burkholderia cenocepacia integrates cis-2-dodecenoic acid and cyclic dimeric guanosine monophosphate signals to control virulence

2017 ◽  
Vol 114 (49) ◽  
pp. 13006-13011 ◽  
Author(s):  
Chunxi Yang ◽  
Chaoyu Cui ◽  
Qiumian Ye ◽  
Jinhong Kan ◽  
Shuna Fu ◽  
...  
Keyword(s):  
Guanosine Monophosphate ◽  
Burkholderia Cenocepacia ◽  
Gene Promoters ◽  
Biological Functions ◽  
Environmental Chemical ◽  
Cell Functions ◽  
Diffusible Signal Factor ◽  
Cyclic Diguanosine Monophosphate ◽  
Diguanosine Monophosphate ◽  
Physical And Chemical

Quorum sensing (QS) signals are used by bacteria to regulate biological functions in response to cell population densities. Cyclic diguanosine monophosphate (c-di-GMP) regulates cell functions in response to diverse environmental chemical and physical signals that bacteria perceive. In Burkholderia cenocepacia, the QS signal receptor RpfR degrades intracellular c-di-GMP when it senses the QS signal cis-2-dodecenoic acid, also called Burkholderia diffusible signal factor (BDSF), as a proxy for high cell density. However, it was unclear how this resulted in control of BDSF-regulated phenotypes. Here, we found that RpfR forms a complex with a regulator named GtrR (BCAL1536) to enhance its binding to target gene promoters under circumstances where the BDSF signal binds to RpfR to stimulate its c-di-GMP phosphodiesterase activity. In the absence of BDSF, c-di-GMP binds to the RpfR-GtrR complex and inhibits its ability to control gene expression. Mutations in rpfR and gtrR had overlapping effects on both the B. cenocepacia transcriptome and BDSF-regulated phenotypes, including motility, biofilm formation, and virulence. These results show that RpfR is a QS signal receptor that also functions as a c-di-GMP sensor. This protein thus allows B. cenocepacia to integrate information about its physical and chemical surroundings as well as its population density to control diverse biological functions including virulence. This type of QS system appears to be widely distributed in beta and gamma proteobacteria.

scholarly journals Degradation of cyclic diguanosine monophosphate by a hybrid two-component protein protects Azoarcus sp. strain CIB from toluene toxicity

2016 ◽  
Vol 113 (46) ◽  
pp. 13174-13179 ◽  
Author(s):  
Zaira Martín-Moldes ◽  
Blas Blázquez ◽  
Claudine Baraquet ◽  
Caroline S. Harwood ◽  
María T. Zamarro ◽  
...  
Keyword(s):  
Aromatic Hydrocarbons ◽  
Response Regulator ◽  
Anaerobic Growth ◽  
Two Component System ◽  
Component System ◽  
Bacterial Physiology ◽  
Toxic Concentration ◽  
Two Component ◽  
Cyclic Diguanosine Monophosphate ◽  
Diguanosine Monophosphate

Cyclic diguanosine monophosphate (c-di-GMP) is a second messenger that controls diverse functions in bacteria, including transitions from planktonic to biofilm lifestyles, virulence, motility, and cell cycle. Here we describe TolR, a hybrid two-component system (HTCS), from the β-proteobacterium Azoarcus sp. strain CIB that degrades c-di-GMP in response to aromatic hydrocarbons, including toluene. This response protects cells from toluene toxicity during anaerobic growth. Whereas wild-type cells tolerated a sudden exposure to a toxic concentration of toluene, a tolR mutant strain or a strain overexpressing a diguanylate cyclase gene lost viability upon toluene shock. TolR comprises an N-terminal aromatic hydrocarbon-sensing Per–Arnt–Sim (PAS) domain, followed by an autokinase domain, a response regulator domain, and a C-terminal c-di-GMP phosphodiesterase (PDE) domain. Autophosphorylation of TolR in response to toluene exposure initiated an intramolecular phosphotransfer to the response regulator domain that resulted in c-di-GMP degradation. The TolR protein was engineered as a functional sensor histidine kinase (TolRSK) and an independent response regulator (TolRRR). This classic two-component system (CTCS) operated less efficiently than TolR, suggesting that TolR was evolved as a HTCS to optimize signal transduction. Our results suggest that TolR enables Azoarcus sp. CIB to adapt to toxic aromatic hydrocarbons under anaerobic conditions by modulating cellular levels of c-di-GMP. This is an additional role for c-di-GMP in bacterial physiology.

The cis -2-dodecenoic acid (BDSF) quorum sensing system in Burkholderia cenocepacia

2022 ◽  
Author(s):  
Mingfang Wang ◽  
Xia Li ◽  
Shihao Song ◽  
Chaoyu Cui ◽  
Lian-Hui Zhang ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Xanthomonas Campestris ◽  
Cell Communication ◽  
Burkholderia Cenocepacia ◽  
Bacterial Cells ◽  
Communication Signals ◽  
Signal Perception ◽  
Sensing System ◽  
Diffusible Signal Factor

It has been demonstrated that quorum sensing (QS) is widely employed by bacterial cells to coordinately regulate various group behaviors. Diffusible signal factor (DSF)-type signals have emerged as a growing family of conserved cell-cell communication signals. In addition to the DSF signal initially identified in Xanthomonas campestris pv. campestris, B urkholderia d iffusible s ignal f actor (BDSF, cis -2-dodecenoic acid) has been recognized as a conserved DSF-type signal with specific characteristics in both signal perception and transduction from DSF signals. Here, we review the history and current progress of the research of this type of signal, especially focusing on its biosynthesis, signaling pathways, and biological functions. We also discuss and explore the huge potential of targeting this kind of QS system as a new therapeutic strategy to control bacterial infections and diseases.

scholarly journals Globins Synthesize the Second Messenger Bis-(3′–5′)-Cyclic Diguanosine Monophosphate in Bacteria

2009 ◽  
Vol 388 (2) ◽  
pp. 262-270 ◽  
Author(s):  
Xuehua Wan ◽  
Jason R. Tuckerman ◽  
Jennifer A. Saito ◽  
Tracey Allen K. Freitas ◽  
James S. Newhouse ◽  
...  
Keyword(s):  
Second Messenger ◽  
Cyclic Diguanosine Monophosphate ◽  
Diguanosine Monophosphate

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 genomic predictor of lifespan in vertebrates

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Benjamin Mayne ◽  
Oliver Berry ◽  
Campbell Davies ◽  
Jessica Farley ◽  
Simon Jarman
Keyword(s):  
Dna Methylation ◽  
Gene Promoters ◽  
Epigenetic Changes ◽  
Ecological Significance ◽  
Biological Functions ◽  
Maximum Lifespan ◽  
Genome Sequences ◽  
Biological Ageing ◽  
Cpg Sites ◽  
Whole Genomes

AbstractBiological ageing and its mechanistic underpinnings are of immense biomedical and ecological significance. Ageing involves the decline of diverse biological functions and places a limit on a species’ maximum lifespan. Ageing is associated with epigenetic changes involving DNA methylation. Furthermore, an analysis of mammals showed that the density of CpG sites in gene promoters, which are targets for DNA methylation, is correlated with lifespan. Using 252 whole genomes and databases of animal age and promotor sequences, we show a pattern across vertebrates. We also derive a predictive lifespan clock based on CpG density in a selected set of promoters. The lifespan clock accurately predicts maximum lifespan in vertebrates (R2 = 0.76) from the density of CpG sites within only 42 selected promoters. Our lifespan clock provides a wholly new method for accurately estimating lifespan using genome sequences alone and enables estimation of this challenging parameter for both poorly understood and extinct species.

The Insights and Perspectives of Nitric Oxide-mediated Biofilm Eradication

2021 ◽  
Vol 21 ◽  
Author(s):  
Mingke Yuan ◽  
Tao Sun ◽  
Jianbing Wu ◽  
Yue Fei ◽  
Yueqi Yang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pathogenic Bacteria ◽  
Drug Sensitivity ◽  
Antimicrobial Agents ◽  
Therapeutic Agents ◽  
Recurrent Infections ◽  
Future Directions ◽  
Drug Permeability ◽  
Cyclic Diguanosine Monophosphate ◽  
Diguanosine Monophosphate

: Biofilms are among the most important causes of nosocomial and recurrent infections as biofilms confer antibiotic resistance to pathogenic bacteria and protect them from the host’s immune system. Thus, it is imperative to investigate effective therapeutic agents to counteract biofilms. As an important signaling molecule, nitric oxide (NO) plays a crucial role in various biological and pathological processes. NO could disperse biofilm and restore the drug sensitivity by reducing intracellular cyclic-diguanosine monophosphate (c-di-GMP) levels. This review highlights recent advances on antibacterial and antibiofilm effects of NO when NO was co-administered with other antimicrobial agents. A significant improvement in drug permeability and biofilm cell targeting and reduced cytotoxicity could be attained with this strategy. In this review, we briefly lay out challenges and propose future directions in this appealing avenue of research on NO-based therapy for biofilm eradication.

scholarly journals Structural and Functional Characterization of Diffusible Signal Factor Family Quorum-Sensing Signals Produced by Members of the Burkholderia cepacia Complex

2010 ◽  
Vol 76 (14) ◽  
pp. 4675-4683 ◽  
Author(s):  
Yinyue Deng ◽  
Ji'en Wu ◽  
Leo Eberl ◽  
Lian-Hui Zhang
Keyword(s):  
Quorum Sensing ◽  
Burkholderia Cepacia ◽  
High Performance ◽  
Xanthomonas Campestris ◽  
Functional Characterization ◽  
Cell Communication ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Communication Signals ◽  
Diffusible Signal Factor

ABSTRACT Previous work has shown that Burkholderia cenocepacia produces the diffusible signal factor (DSF) family signal cis-2-dodecenoic acid (C12:Δ2, also known as BDSF), which is involved in the regulation of virulence. In this study, we determined whether C12:Δ2 production is conserved in other members of the Burkholderia cepacia complex (Bcc) by using a combination of high-performance liquid chromatography, mass spectrometry, and bioassays. Our results show that five Bcc species are capable of producing C12:Δ2 as a sole DSF family signal, while four species produce not only C12:Δ2 but also a new DSF family signal, which was identified as cis,cis-11-methyldodeca-2,5-dienoic acid (11-Me-C12:Δ2,5). In addition, we demonstrate that the quorum-sensing signal cis-11-methyl-2-dodecenoic acid (11-Me-C12:Δ2), which was originally identified in Xanthomonas campestris supernatants, is produced by Burkholderia multivorans. It is shown that, similar to 11-Me-C12:Δ2 and C12:Δ2, the newly identified molecule 11-Me-C12:Δ2,5 is a potent signal in the regulation of biofilm formation, the production of virulence factors, and the morphological transition of Candida albicans. These data provide evidence that DSF family molecules are highly conserved bacterial cell-cell communication signals that play key roles in the ecology of the organisms that produce them.

scholarly journals Insight into Mechanobiology: How Stem Cells Feel Mechanical Forces and Orchestrate Biological Functions

2019 ◽  
Vol 20 (21) ◽  
pp. 5337 ◽  
Author(s):  
Chiara Argentati ◽  
Francesco Morena ◽  
Ilaria Tortorella ◽  
Martina Bazzucchi ◽  
Serena Porcellati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Active Role ◽  
Biological Functions ◽  
Cell Functions ◽  
Dynamic Relationship ◽  
Physical Stimuli

The cross-talk between stem cells and their microenvironment has been shown to have a direct impact on stem cells’ decisions about proliferation, growth, migration, and differentiation. It is well known that stem cells, tissues, organs, and whole organisms change their internal architecture and composition in response to external physical stimuli, thanks to cells’ ability to sense mechanical signals and elicit selected biological functions. Likewise, stem cells play an active role in governing the composition and the architecture of their microenvironment. Is now being documented that, thanks to this dynamic relationship, stemness identity and stem cell functions are maintained. In this work, we review the current knowledge in mechanobiology on stem cells. We start with the description of theoretical basis of mechanobiology, continue with the effects of mechanical cues on stem cells, development, pathology, and regenerative medicine, and emphasize the contribution in the field of the development of ex-vivo mechanobiology modelling and computational tools, which allow for evaluating the role of forces on stem cell biology.

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