A LuxS-Dependent Cell-to-Cell Language Regulates Social Behavior and Development in Bacillus subtilis

ABSTRACT Cell-to-cell communication in bacteria is mediated by quorum-sensing systems (QSS) that produce chemical signal molecules called autoinducers (AI). In particular, LuxS/AI-2-dependent QSS has been proposed to act as a universal lexicon that mediates intra- and interspecific bacterial behavior. Here we report that the model organism Bacillus subtilis operates a luxS-dependent QSS that regulates its morphogenesis and social behavior. We demonstrated that B. subtilis luxS is a growth-phase-regulated gene that produces active AI-2 able to mediate the interspecific activation of light production in Vibrio harveyi. We demonstrated that in B. subtilis, luxS expression was under the control of a novel AI-2-dependent negative regulatory feedback loop that indicated an important role for AI-2 as a signaling molecule. Even though luxS did not affect spore development, AI-2 production was negatively regulated by the master regulatory proteins of pluricellular behavior, SinR and Spo0A. Interestingly, wild B. subtilis cells, from the undomesticated and probiotic B. subtilis natto strain, required the LuxS-dependent QSS to form robust and differentiated biofilms and also to swarm on solid surfaces. Furthermore, LuxS activity was required for the formation of sophisticated aerial colonies that behaved as giant fruiting bodies where AI-2 production and spore morphogenesis were spatially regulated at different sites of the developing colony. We proposed that LuxS/AI-2 constitutes a novel form of quorum-sensing regulation where AI-2 behaves as a morphogen-like molecule that coordinates the social and pluricellular behavior of B. subtilis.

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The impact of quorum sensing on the modulation of phage-host interactions

Journal of Bacteriology ◽

10.1128/jb.00687-20 ◽

2021 ◽

Author(s):

Josefina León-Félix ◽

Claudia Villicaña

Keyword(s):

Quorum Sensing ◽

Cell Communication ◽

Signal Molecules ◽

Term Survival ◽

Intrinsic Factors ◽

Host Interactions ◽

Defensive Strategies ◽

The Social ◽

Biological Entities ◽

The Impact

Bacteriophages are the most diverse and abundant biological entities on the Earth and require host bacteria to replicate. Because of this obligate relationship, in addition to the challenging conditions of surrounding environments, phages must integrate information about extrinsic and intrinsic factors when infecting their host. This integration helps to determine whether the infection becomes lytic or lysogenic, which likely influences phage spreading and long-term survival. Although a variety of environmental and physiological clues are known to modulate lysis-lysogeny decisions, the social interplay among phages and host populations has been overlooked until recently. A growing body of evidence indicates that cell-cell communication in bacteria and, more recently, peptide-based communication among phage-phage populations, affect phage-host interactions by controlling phage lysis-lysogeny decisions and phage counter-defensive strategies in bacteria. Here, we explore and discuss the role of signal molecules as well as quorum sensing and quenching factors that mediate phage-host interactions. Our aim is to provide an overview of population-dependent mechanisms that influence phage replication, and how social communication may affect the dynamics and evolution of microbial communities, including their implications in phage therapy.

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Peptide signaling without feedback in signal production operates as a true quorum sensing communication system in Bacillus subtilis

Communications Biology ◽

10.1038/s42003-020-01553-5 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Iztok Dogsa ◽

Mihael Spacapan ◽

Anna Dragoš ◽

Tjaša Danevčič ◽

Žiga Pandur ◽

...

Keyword(s):

Gene Expression ◽

Bacillus Subtilis ◽

Quorum Sensing ◽

Cell Density ◽

Communication System ◽

Communication Systems ◽

Feedback Loop ◽

Signal Molecules ◽

Specific Cell ◽

Sharp Transition

AbstractBacterial quorum sensing (QS) is based on signal molecules (SM), which increase in concentration with cell density. At critical SM concentration, a variety of adaptive genes sharply change their expression from basic level to maximum level. In general, this sharp transition, a hallmark of true QS, requires an SM dependent positive feedback loop, where SM enhances its own production. Some communication systems, like the peptide SM-based ComQXPA communication system of Bacillus subtilis, do not have this feedback loop and we do not understand how and if the sharp transition in gene expression is achieved. Based on experiments and mathematical modeling, we observed that the SM peptide ComX encodes the information about cell density, specific cell growth rate, and even oxygen concentration, which ensure power-law increase in SM production. This enables together with the cooperative response to SM (ComX) a sharp transition in gene expression level and this without the SM dependent feedback loop. Due to its ultra-sensitive nature, the ComQXPA can operate at SM concentrations that are 100–1000 times lower than typically found in other QS systems, thereby substantially reducing the total metabolic cost of otherwise expensive ComX peptide.

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Quorum sensing and social networking in the microbial world

Journal of The Royal Society Interface ◽

10.1098/rsif.2009.0203 ◽

2009 ◽

Vol 6 (40) ◽

pp. 959-978 ◽

Cited By ~ 258

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.

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

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2007.2039 ◽

2007 ◽

Vol 362 (1483) ◽

pp. 1119-1134 ◽

Cited By ~ 509

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.

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Saccharomyces cerevisiae Requires CFF1 To Produce 4-Hydroxy-5-Methylfuran-3(2H)-One, a Mimic of the Bacterial Quorum-Sensing Autoinducer AI-2

mBio ◽

10.1128/mbio.03303-20 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Julie S. Valastyan ◽

Christina M. Kraml ◽

Istvan Pelczer ◽

Thomas Ferrante ◽

Bonnie L. Bassler

Keyword(s):

Saccharomyces Cerevisiae ◽

Quorum Sensing ◽

Bacterial Species ◽

Cell Communication ◽

Communication Process ◽

Signal Molecules ◽

Catalytic Residue ◽

Interspecies Communication ◽

Content Type ◽

Extracellular Signal

ABSTRACT Quorum sensing is a process of cell-to-cell communication that bacteria use to orchestrate collective behaviors. Quorum sensing depends on the production, release, and detection of extracellular signal molecules called autoinducers (AIs) that accumulate with increasing cell density. While most AIs are species specific, the AI called AI-2 is produced and detected by diverse bacterial species, and it mediates interspecies communication. We recently reported that mammalian cells produce an AI-2 mimic that can be detected by bacteria through the AI-2 receptor LuxP, potentially expanding the role of the AI-2 system to interdomain communication. Here, we describe a second molecule capable of interdomain signaling through LuxP, 4-hydroxy-5-methylfuran-3(2H)-one (MHF), that is produced by the yeast Saccharomyces cerevisiae. Screening the S. cerevisiae deletion collection revealed Cff1p, a protein with no known role, to be required for MHF production. Cff1p is proposed to be an enzyme, with structural similarity to sugar isomerases and epimerases, and substitution at the putative catalytic residue eliminated MHF production in S. cerevisiae. Sequence analysis uncovered Cff1p homologs in many species, primarily bacterial and fungal, but also viral, archaeal, and higher eukaryotic. Cff1p homologs from organisms from all domains can complement a cff1Δ S. cerevisiae mutant and restore MHF production. In all cases tested, the identified catalytic residue is conserved and required for MHF to be produced. These findings increase the scope of possibilities for interdomain interactions via AI-2 and AI-2 mimics, highlighting the breadth of molecules and organisms that could participate in quorum sensing. IMPORTANCE Quorum sensing is a cell-to-cell communication process that bacteria use to monitor local population density. Quorum sensing relies on extracellular signal molecules called autoinducers (AIs). One AI called AI-2 is broadly made by bacteria and used for interspecies communication. Here, we describe a eukaryotic AI-2 mimic, 4-hydroxy-5-methylfuran-3(2H)-one, (MHF), that is made by the yeast Saccharomyces cerevisiae, and we identify the Cff1p protein as essential for MHF production. Hundreds of viral, archaeal, bacterial, and eukaryotic organisms possess Cff1p homologs. This finding, combined with our results showing that homologs from all domains can replace S. cerevisiae Cff1p, suggests that like AI-2, MHF is widely produced. Our results expand the breadth of organisms that may participate in quorum-sensing-mediated interactions.

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Microfluidic static droplet array for analyzing microbial communication on a population gradient

Lab on a Chip ◽

10.1039/c4lc01097c ◽

2015 ◽

Vol 15 (3) ◽

pp. 889-899 ◽

Cited By ~ 39

Author(s):

Heon-Ho Jeong ◽

Si Hyung Jin ◽

Byung Jin Lee ◽

Taesung Kim ◽

Chang-Soo Lee

Keyword(s):

Quorum Sensing ◽

Population Density ◽

Cell Communication ◽

Signal Molecules ◽

Microbial Communication ◽

Droplet Array ◽

Cell Cell

Quorum sensing (QS) is a type of cell–cell communication using signal molecules that are released and detected by cells, which respond to changes in their population density.

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Quorum Sensing Regulation as a Target for Antimicrobial Therapy

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666211202115259 ◽

2021 ◽

Vol 21 ◽

Author(s):

Caterine Henríquez Ruiz ◽

Estefanie Osorio-Llanes ◽

Mayra Hernández Trespalacios ◽

Evelyn Mendoza-Torres ◽

Wendy Rosales ◽

...

Keyword(s):

Quorum Sensing ◽

Molecular Mechanisms ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Bacterial Species ◽

Cell Communication ◽

Structural Evolution ◽

Structural Diversity ◽

Signal Molecules ◽

Bacterial Survival

: Some bacterial species use a cell-to-cell communication mechanism called Quorum Sensing (QS). Bacteria release small diffusible molecules, usually termed signals which allow the activation of beneficial phenotypes that guarantee bacterial survival and the expression of a diversity of virulence genes in response to an increase in population density. The study of the molecular mechanisms that relate signal molecules with bacterial pathogenesis is an area of growing interest due to its use as a possible therapeutic alternative through the development of synthetic analogues of autoinducers as a strategy to regulate bacterial communication as well as the study of bacterial resistance phenomena, the study of these relationships is based on the structural diversity of natural or synthetic autoinducers and their ability to inhibit bacterial QS, which can be approached with a molecular perspective from the following topics: i) Molecular signals and their role in QS regulation; ii) Strategies in the modulation of Quorum Sensing; iii) Analysis of Bacterial QS circuit regulation strategies; iv) Structural evolution of natural and synthetic autoinducers as QS regulators. This mini-review allows a molecular view of the QS systems, showing a perspective on the importance of the molecular diversity of autoinducer analogs as a strategy for the design of new antimicrobial agents.

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Quorum sensing and the population-dependent control of virulence

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2000.0607 ◽

2000 ◽

Vol 355 (1397) ◽

pp. 667-680 ◽

Cited By ~ 167

Author(s):

Paul Williams ◽

Miguel Camara ◽

Andrea Hardman ◽

Simon Swift ◽

Deborah Milton ◽

...

Keyword(s):

Quorum Sensing ◽

Population Density ◽

Cell Population ◽

Cell Communication ◽

Immunomodulatory Activity ◽

Signal Molecules ◽

Dependent Manner ◽

Virulence Determinants ◽

Signal Molecule ◽

Cell Cell

One crucial feature of almost all bacterial infections is the need for the invading pathogen to reach a critical cell population density sufficient to overcome host defences and establish the infection. Controlling the expression of virulence determinants in concert with cell population density may therefore confer a significant survival advantage on the pathogen such that the host is overwhelmed before a defence response can be fully initiated. Many different bacterial pathogens are now known to regulate diverse physiological processes including virulence in a cell–density–dependent manner through cell–cell communication. This phenomenon, which relies on the interaction of a diffusible signal molecule (e.g. an N –acylhomoserine lactone) with a sensor or transcriptional activator to couple gene expression with cell population density, has become known as ‘quorum sensing’ . Although the size of the ‘quorum’ is likely to be highly variable and influenced by the diffusibility of the signal molecule within infected tissues, nevertheless quorum–sensing signal molecules can be detected in vivo in both experimental animal model and human infections. Furthermore, certain quorum–sensing molecules have been shown to possess pharmacological and immunomodulatory activity such that they may function as virulence determinants per se . As a consequence, quorum sensing constitutes a novel therapeutic target for the design of small molecular antagonists capable of attenuating virulence through the blockade of bacterial cell–cell communication.

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Mathematical Modeling of Zebrafish Social Behavior in Response to Acute Caffeine Administration

Frontiers in Applied Mathematics and Statistics ◽

10.3389/fams.2021.751351 ◽

2021 ◽

Vol 7 ◽

Author(s):

Mohammad Tuqan ◽

Maurizio Porfiri

Keyword(s):

Mathematical Model ◽

Social Behavior ◽

Model Organism ◽

Water Tank ◽

Psychoactive Substances ◽

Preclinical Research ◽

The Social ◽

The Mathematical Model ◽

Potential Use ◽

Turn Rate

Zebrafish is a model organism that is receiving considerable attention in preclinical research. Particularly important is the use of zebrafish in behavioral pharmacology, where a number of high-throughput experimental paradigms have been proposed to quantify the effect of psychoactive substances consequences on individual and social behavior. In an effort to assist experimental research and improve animal welfare, we propose a mathematical model for the social behavior of groups of zebrafish swimming in a shallow water tank in response to the administration of psychoactive compounds to select individuals. We specialize the mathematical model to caffeine, a popular anxiogenic compound. Each fish is assigned to a Markov chain that describes transitions between freezing and swimming. When swimming, zebrafish locomotion is modeled as a pair of coupled stochastic differential equations, describing the time evolution of the turn-rate and speed in response to caffeine administration. Comparison with experimental results demonstrates the accuracy of the model and its potential use in the design of in-silico experiments.

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Phage-Encoded LuxR-Type Receptors Responsive to Host-Produced Bacterial Quorum-Sensing Autoinducers

10.1101/577726 ◽

2019 ◽

Cited By ~ 1

Author(s):

Justin E. Silpe ◽

Bonnie L. Bassler

Keyword(s):

Quorum Sensing ◽

Pathogenic Bacteria ◽

Cell Communication ◽

Signal Molecules ◽

Host Bacterium ◽

Gram Negative ◽

Collective Behaviors ◽

Bacterial Quorum Sensing ◽

Genes Encoding ◽

Bacterial Quorum

AbstractQuorum sensing (QS) is a process of cell-to-cell communication that bacteria use to orchestrate collective behaviors. QS relies on the cell-density-dependent production, accumulation, and receptor-mediated detection of extracellular signaling molecules called autoinducers (AIs). Gram-negative bacteria commonly use N-acyl homoserine lactones (AHLs) as their AIs and they are detected by LuxR-type receptors. Often, LuxR-type receptors are insoluble when not bound to a cognate AI. In this report, we show that LuxR-type receptors are encoded on phage genomes and, in the cases we tested, the phage LuxR-type receptors bind to and are solubilized specifically by the AHL AI produced by the host bacterium. We do not yet know the viral activities that are controlled by these phage QS receptors, however, our observations, coupled with recent reports, suggest that their occurrence is more widespread than previously appreciated. Using receptor-mediated detection of QS AIs could enable phages to garner information concerning the population density status of their bacterial hosts. We speculate that such information can be exploited by phages to optimize the timing of execution of particular steps in viral infection.ImportanceBacteria communicate with chemical signal molecules to regulate group behaviors in a process called quorum sensing (QS). In this report, we find that genes encoding receptors for Gram-negative bacterial QS communication molecules are present on genomes of viruses that infect these bacteria. These viruses are called phages. We show that two phage-encoded receptors, like their bacterial counterparts, bind to the communication molecule produced by the host bacterium, suggesting that phages can “listen in” on their bacterial hosts. Interfering with bacterial QS and using phages to kill pathogenic bacteria represent attractive possibilities for development of new antimicrobials to combat pathogens that are resistant to traditional antibiotics. Our findings of interactions between phages and QS bacteria need consideration as new antimicrobial therapies are developed.

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