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 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 The roles of histidine kinases in sensing host plant and cell–cell communication signal in a phytopathogenic bacterium

2019 ◽  
Vol 374 (1767) ◽  
pp. 20180311 ◽  
Author(s):  
Fang-Fang Wang ◽  
Wei Qian
Keyword(s):  
Xanthomonas Campestris ◽  
Cell Communication ◽  
Research Progress ◽  
Bacterial Cells ◽  
Histidine Kinases ◽  
Phytopathogenic Bacterium ◽  
Bacterial Diseases ◽  
Signal Perception ◽  
Communication Signal ◽  
Diffusible Signal Factor

It has long been known that phytopathogenic bacteria react to plant-specific stimuli or environmental factors. However, how bacterial cells sense these environmental cues remains incompletely studied. Recently, three kinds of histidine kinases (HKs) were identified as receptors to perceive plant-associated or quorum-sensing signals. Among these kinases, HK VgrS detects iron depletion by binding to ferric iron via an ExxE motif, RpfC binds diffusible signal factor (DSF) by its N-terminal peptide and activates its autokinase activity through relaxation of autoinhibition, and PcrK specifically senses plant hormone–cytokinin and elicits bacterial responses to oxidative stress. These HKs are critical sensors that regulate the virulence of a Gram-negative bacterium, Xanthomonas campestris pv. campestris . Research progress on the signal perception of phytopathogenic bacterial HKs suggests that inter-kingdom signalling between host plants and pathogens controls pathogenesis and can be used as a potential molecular target to protect plants from bacterial diseases. This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management’.

scholarly journals Identification of FadT as a Novel Quorum Quenching Enzyme for the Degradation of Diffusible Signal Factor in Cupriavidus pinatubonensis Strain HN-2

2021 ◽  
Vol 22 (18) ◽  
pp. 9862
Author(s):  
Xudan Xu ◽  
Tian Ye ◽  
Wenping Zhang ◽  
Tian Zhou ◽  
Xiaofan Zhou ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Xanthomonas Campestris ◽  
Cell Communication ◽  
Maximal Activity ◽  
Quorum Quenching ◽  
Site Directed Mutagenesis ◽  
Diffusible Signal Factor ◽  
High Enzymatic Activity ◽  
Xanthomonas Campestris Pv Campestris ◽  
Potential Use

Quorum sensing (QS) is a microbial cell–cell communication mechanism and plays an important role in bacterial infections. QS-mediated bacterial infections can be blocked through quorum quenching (QQ), which hampers signal accumulation, recognition, and communication. The pathogenicity of numerous bacteria, including Xanthomonas campestris pv. campestris (Xcc), is regulated by diffusible signal factor (DSF), a well-known fatty acid signaling molecule of QS. Cupriavidus pinatubonensis HN-2 could substantially attenuate the infection of XCC through QQ by degrading DSF. The QQ mechanism in strain HN-2, on the other hand, is yet to be known. To understand the molecular mechanism of QQ in strain HN-2, we used whole-genome sequencing and comparative genomics studies. We discovered that the fadT gene encodes acyl-CoA dehydrogenase as a novel QQ enzyme. The results of site-directed mutagenesis demonstrated the requirement of fadT gene for DSF degradation in strain HN-2. Purified FadT exhibited high enzymatic activity and outstanding stability over a broad pH and temperature range with maximal activity at pH 7.0 and 35 °C. No cofactors were required for FadT enzyme activity. The enzyme showed a strong ability to degrade DSF. Furthermore, the expression of fadT in Xcc results in a significant reduction in the pathogenicity in host plants, such as Chinese cabbage, radish, and pakchoi. Taken together, our results identified a novel DSF-degrading enzyme, FadT, in C. pinatubonensis HN-2, which suggests its potential use in the biological control of DSF-mediated pathogens.

scholarly journals Cis-2-dodecenoic acid receptor RpfR links quorum-sensing signal perception with regulation of virulence through cyclic dimeric guanosine monophosphate turnover

2012 ◽  
Vol 109 (38) ◽  
pp. 15479-15484 ◽  
Author(s):  
Yinyue Deng ◽  
Nadine Schmid ◽  
Chao Wang ◽  
Jianhe Wang ◽  
Gabriella Pessi ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Conformational Changes ◽  
Biofilm Formation ◽  
Xanthomonas Campestris ◽  
Guanosine Monophosphate ◽  
Burkholderia Cenocepacia ◽  
Receptor Protein ◽  
Bacterial Physiology ◽  
Signal Perception ◽  
Mutant Phenotypes

Many bacterial pathogens produce diffusible signal factor (DSF)-type quorum sensing (QS) signals in modulation of virulence and biofilm formation. Previous work on Xanthomonas campestris showed that the RpfC/RpfG two-component system is involved in sensing and responding to DSF signals, but little is known in other microorganisms. Here we show that in Burkholderia cenocepacia the DSF-family signal cis-2-dodecenoic acid (BDSF) negatively controls the intracellular cyclic dimeric guanosine monophosphate (c-di-GMP) level through a receptor protein RpfR, which contains Per/Arnt/Sim (PAS)-GGDEF-EAL domains. RpfR regulates the same phenotypes as BDSF including swarming motility, biofilm formation, and virulence. In addition, the BDSF− mutant phenotypes could be rescued by in trans expression of RpfR, or its EAL domain that functions as a c-di-GMP phosphodiesterase. BDSF is shown to bind to the PAS domain of RpfR with high affinity and stimulates its phosphodiesterase activity through induction of allosteric conformational changes. Our work presents a unique and widely conserved DSF-family signal receptor that directly links the signal perception to c-di-GMP turnover in regulation of bacterial physiology.

scholarly journals Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Orit Malka ◽  
Dorin Kalson ◽  
Karin Yaniv ◽  
Reut Shafir ◽  
Manikandan Rajendran ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Gut Microbiome ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Human Microbiome ◽  
Cell Communication ◽  
Probiotic Yeast ◽  
Gut Pathogen ◽  
Cell Cell

Abstract Background Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. Results The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite—tryptophol acetate—which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. Conclusions This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule—tryptophol acetate—was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases.

scholarly journals Disruption of Quorum Sensing and Virulence inBurkholderia cenocepaciaby a Structural Analogue of thecis-2-Dodecenoic Acid Signal

2019 ◽  
Vol 85 (8) ◽  
Author(s):  
Chaoyu Cui ◽  
Shihao Song ◽  
Chunxi Yang ◽  
Xiuyun Sun ◽  
Yutong Huang ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Burkholderia Cenocepacia ◽  
Enoic Acid ◽  
Acyl Homoserine Lactone ◽  
Structural Analogue ◽  
Content Type ◽  
Signal Production

ABSTRACTQuorum sensing (QS) signals are widely used by bacterial pathogens to control biological functions and virulence in response to changes in cell population densities.Burkholderia cenocepaciaemploys a molecular mechanism in which thecis-2-dodecenoic acid (namedBurkholderiadiffusiblesignalfactor [BDSF]) QS system regulatesN-acyl homoserine lactone (AHL) signal production and virulence by modulating intracellular levels of cyclic diguanosine monophosphate (c-di-GMP). Thus, inhibition of BDSF signaling may offer a non-antibiotic-based therapeutic strategy against BDSF-regulated bacterial infections. In this study, we report the synthesis of small-molecule mimics of the BDSF signal and evaluate their ability to inhibit BDSF QS signaling inB. cenocepacia. A novel structural analogue of BDSF, 14-Me-C16:Δ2(cis-14-methylpentadec-2-enoic acid), was observed to inhibit BDSF production and impair BDSF-regulated phenotypes inB. cenocepacia, including motility, biofilm formation, and virulence, while it did not inhibit the growth rate of this pathogen. 14-Me-C16:Δ2also reduced AHL signal production. Genetic and biochemical analyses showed that 14-Me-C16:Δ2inhibited the production of the BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Notably, 14-Me-C16:Δ2attenuated BDSF-regulated phenotypes in variousBurkholderiaspecies. These findings suggest that 14-Me-C16:Δ2could potentially be developed as a new therapeutic agent against pathogenicBurkholderiaspecies by interfering with their QS signaling.IMPORTANCEBurkholderia cenocepaciais an important opportunistic pathogen which can cause life-threatening infections in susceptible individuals, particularly in cystic fibrosis and immunocompromised patients. It usually employs two types of quorum sensing (QS) systems, including thecis-2-dodecenoic acid (BDSF) system andN-acyl homoserine lactone (AHL) system, to regulate virulence. In this study, we have designed and identified an unsaturated fatty acid compound (cis-14-methylpentadec-2-enoic acid [14-Me-C16:Δ2]) that is capable of interfering withB. cenocepaciaQS signaling and virulence. We demonstrate that 14-Me-C16:Δ2reduced BDSF and AHL signal production inB. cenocepacia. It also impaired QS-regulated phenotypes in variousBurkholderiaspecies. These results suggest that 14-Me-C16:Δ2could interfere with QS signaling in manyBurkholderiaspecies and might be developed as a new antibacterial agent.

scholarly journals Quorum sensing and social networking in the microbial world

2009 ◽  
Vol 6 (40) ◽  
pp. 959-978 ◽  
Author(s):  
Steve Atkinson ◽  
Paul Williams
Keyword(s):  
Quorum Sensing ◽  
Social Networking ◽  
Communication Networks ◽  
Cell Communication ◽  
Signal Molecules ◽  
Gram Negative Bacteria ◽  
Bacterial Cells ◽  
Microbial World ◽  
Rich Diversity ◽  
Intercellular Signalling

For many years, bacterial cells were considered primarily as selfish individuals, but, in recent years, it has become evident that, far from operating in isolation, they coordinate collective behaviour in response to environmental challenges using sophisticated intercellular communication networks. Cell-to-cell communication between bacteria is mediated by small diffusible signal molecules that trigger changes in gene expression in response to fluctuations in population density. This process, generally referred to as quorum sensing (QS), controls diverse phenotypes in numerous Gram-positive and Gram-negative bacteria. Recent advances have revealed that bacteria are not limited to communication within their own species but are capable of ‘listening in’ and ‘broadcasting to’ unrelated species to intercept messages and coerce cohabitants into behavioural modifications, either for the good of the population or for the benefit of one species over another. It is also evident that QS is not limited to the bacterial kingdom. The study of two-way intercellular signalling networks between bacteria and both uni- and multicellular eukaryotes as well as between eukaryotes is just beginning to unveil a rich diversity of communication pathways.

scholarly journals Look who's talking: communication and quorum sensing in the bacterial world

2007 ◽  
Vol 362 (1483) ◽  
pp. 1119-1134 ◽  
Author(s):  
Paul Williams ◽  
Klaus Winzer ◽  
Weng C Chan ◽  
Miguel Cámara
Keyword(s):  
Quorum Sensing ◽  
Bacterial Population ◽  
Response Regulator ◽  
Cell Communication ◽  
Threshold Concentration ◽  
Critical Threshold ◽  
Signal Molecules ◽  
Bacterial Cells ◽  
Environmental Threats ◽  
Generic Term

For many years bacteria were considered primarily as autonomous unicellular organisms with little capacity for collective behaviour. However, we now appreciate that bacterial cells are in fact, highly communicative. The generic term ‘quorum sensing’ has been adopted to describe the bacterial cell-to-cell communication mechanisms which co-ordinate gene expression usually, but not always, when the population has reached a high cell density. Quorum sensing depends on the synthesis of small molecules (often referred to as pheromones or autoinducers) that diffuse in and out of bacterial cells. As the bacterial population density increases, so does the synthesis of quorum sensing signal molecules, and consequently, their concentration in the external environment rises. Once a critical threshold concentration has been reached, a target sensor kinase or response regulator is activated (or repressed) so facilitating the expression of quorum sensing-dependent genes. Quorum sensing enables a bacterial population to mount a co-operative response that improves access to nutrients or specific environmental niches, promotes collective defence against other competitor prokaryotes or eukaryotic defence mechanisms and facilitates survival through differentiation into morphological forms better able to combat environmental threats. Quorum sensing also crosses the prokaryotic–eukaryotic boundary since quorum sensing-dependent signalling can be exploited or inactivated by both plants and mammals.

scholarly journals Bacterial Quorum Sensing and Microbial Community Interactions

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Rhea G. Abisado ◽  
Saida Benomar ◽  
Jennifer R. Klaus ◽  
Ajai A. Dandekar ◽  
Josephine R. Chandler
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Microbial Interactions ◽  
Community Interactions ◽  
Bacterial Populations ◽  
Bacterial Quorum Sensing ◽  
A Cell ◽  
Bacterial Quorum

ABSTRACTMany bacteria use a cell-cell communication system called quorum sensing to coordinate population density-dependent changes in behavior. Quorum sensing involves production of and response to diffusible or secreted signals, which can vary substantially across different types of bacteria. In many species, quorum sensing modulates virulence functions and is important for pathogenesis. Over the past half-century, there has been a significant accumulation of knowledge of the molecular mechanisms, signal structures, gene regulons, and behavioral responses associated with quorum-sensing systems in diverse bacteria. More recent studies have focused on understanding quorum sensing in the context of bacterial sociality. Studies of the role of quorum sensing in cooperative and competitive microbial interactions have revealed how quorum sensing coordinates interactions both within a species and between species. Such studies of quorum sensing as a social behavior have relied on the development of “synthetic ecological” models that use nonclonal bacterial populations. In this review, we discuss some of these models and recent advances in understanding how microbes might interact with one another using quorum sensing. The knowledge gained from these lines of investigation has the potential to guide studies of microbial sociality in natural settings and the design of new medicines and therapies to treat bacterial infections.

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