scholarly journals In silicobacteria evolve robust cooperation via complex quorum-sensing strategies

2019 ◽  
Author(s):  
Yifei Wang ◽  
Jennifer B. Rattray ◽  
Stephen A. Thomas ◽  
James Gurney ◽  
Sam P. Brown
Keyword(s):  
Quorum Sensing ◽  
Experimental Evolution ◽  
Molecular Mechanisms ◽  
Bacterial Species ◽  
Critical Role ◽  
Experimental Studies ◽  
Environmental Drivers ◽  
High Signal ◽  
Environmental Challenges ◽  
Digital Organisms

AbstractMany species of bacteria collectively sense and respond to their social and physical environment via ‘quorum sensing’ (QS), a communication system controlling extracellular cooperative traits. Despite detailed understanding of the mechanisms of signal production and response, there remains considerable debate over the functional role(s) of QS: in short, what is it for? Experimental studies have found support for diverse functional roles: density sensing, mass-transfer sensing, genotype sensing, etc. While consistent with theory, these results cannot separate whether these functions were drivers of QS adaption, or simply artifacts or ‘spandrels’ of systems shaped by distinct ecological pressures. The challenge of separating spandrels from drivers of adaptation is particularly hard to address using extant bacterial species with poorly understood current ecologies (let alone their ecological histories). To understand the relationship between environmental challenges and trajectories of QS evolution, we used an agent-based simulation modeling approach. Given genetic mixing, our simulations produce behaviors that recapitulate features of diverse microbial QS systems, including coercive (high signal / low response) and generalized reciprocity (signal auto-regulation) strategists — that separately and in combination contribute to QS-dependent resilience of QS-controlled cooperation in the face of diverse cheats. We contrast ourin silicoresults with bacterial QS architectures that have evolved under largely unknown ecological contexts, highlighting the critical role of genetic constraints in shaping the shorter term (experimental evolution) dynamics of QS. More broadly, we see experimental evolution of digital organisms as a complementary tool in the search to understand the emergence of complex QS architectures and functions.Author summaryBacteria communicate and cooperate using complex cell-cell signaling systems known as quorum-sensing (QS). While the molecular mechanisms are often well understood, the reasons why bacteria use QS are less clear — how has QS aided survival and growth? The answer to this question is dependent on the environment of adaptation, and unfortunately our current understanding of QS bacterial ecology is broadly lacking. To address this gap, we studied the evolution of ‘digital organisms’, individual-based computer simulations of bacterial populations evolving under defined environmental contexts. Our results pinpoint how simple environmental challenges (variable density and genetic mixing) can lead to the emergence of complex strategies that recapitulate features of bacterial QS, and open a path towards reverse-engineering the environmental drivers of QS.

Modulation of Gut Microbiota through Dietary Phytochemicals as a Novel Anti-infective Strategy

2020 ◽  
Vol 17 (4) ◽  
pp. 498-506 ◽  
Author(s):  
Pavan K. Mujawdiya ◽  
Suman Kapur
Keyword(s):  
Microbial Community ◽  
Quorum Sensing ◽  
Population Density ◽  
Gut Microbiota ◽  
Biofilm Formation ◽  
Chemical Interaction ◽  
Bacterial Species ◽  
Critical Role ◽  
Bacterial Cells ◽  
Gut Microbes

: Quorum Sensing (QS) is a phenomenon in which bacterial cells communicate with each other with the help of several low molecular weight compounds. QS is largely dependent on population density, and it triggers when the concentration of quorum sensing molecules accumulate in the environment and crosses a particular threshold. Once a certain population density is achieved and the concentration of molecules crosses a threshold, the bacterial cells show a collective behavior in response to various chemical stimuli referred to as “auto-inducers”. The QS signaling is crucial for several phenotypic characteristics responsible for bacterial survival such as motility, virulence, and biofilm formation. Biofilm formation is also responsible for making bacterial cells resistant to antibiotics. : The human gut is home to trillions of bacterial cells collectively called “gut microbiota” or “gut microbes”. Gut microbes are a consortium of more than 15,000 bacterial species and play a very crucial role in several body functions such as metabolism, development and maturation of the immune system, and the synthesis of several essential vitamins. Due to its critical role in shaping human survival and its modulating impact on body metabolisms, the gut microbial community has been referred to as “the forgotten organ” by O`Hara et al. (2006) [1]. Several studies have demonstrated that chemical interaction between the members of bacterial cells in the gut is responsible for shaping the overall microbial community. : Recent advances in phytochemical research have generated a lot of interest in finding new, effective, and safer alternatives to modern chemical-based medicines. In the context of antimicrobial research various plant extracts have been identified with Quorum Sensing Inhibitory (QSI) activities among bacterial cells. This review focuses on the mechanism of quorum sensing and quorum sensing inhibitors isolated from natural sources.

scholarly journals Bacterial Quorum-Quenching Lactonase Hydrolyzes Fungal Mycotoxin and Reduces Pathogenicity of Penicillium expansum—Suggesting a Mechanism of Bacterial Antagonism

2021 ◽  
Vol 7 (10) ◽  
pp. 826
Author(s):  
Shlomit Dor ◽  
Dov Prusky ◽  
Livnat Afriat-Jurnou
Keyword(s):  
Cell Wall ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Molecular Mechanisms ◽  
Recombinant Expression ◽  
Bacterial Species ◽  
Quorum Quenching ◽  
Host Cells ◽  
Penicillium Expansum ◽  
Fungal Colonization

Penicillium expansum is a necrotrophic wound fungal pathogen that secrets virulence factors to kill host cells including cell wall degrading enzymes (CWDEs), proteases, and mycotoxins such as patulin. During the interaction between P. expansum and its fruit host, these virulence factors are strictly modulated by intrinsic regulators and extrinsic environmental factors. In recent years, there has been a rapid increase in research on the molecular mechanisms of pathogenicity in P. expansum; however, less is known regarding the bacteria–fungal communication in the fruit environment that may affect pathogenicity. Many bacterial species use quorum-sensing (QS), a population density-dependent regulatory mechanism, to modulate the secretion of quorum-sensing signaling molecules (QSMs) as a method to control pathogenicity. N-acyl homoserine lactones (AHLs) are Gram-negative QSMs. Therefore, QS is considered an antivirulence target, and enzymes degrading these QSMs, named quorum-quenching enzymes, have potential antimicrobial properties. Here, we demonstrate that a bacterial AHL lactonase can also efficiently degrade a fungal mycotoxin. The mycotoxin is a lactone, patulin secreted by fungi such as P. expansum. The bacterial lactonase hydrolyzed patulin at high catalytic efficiency, with a kcat value of 0.724 ± 0.077 s−1 and KM value of 116 ± 33.98 μM. The calculated specific activity (kcat/KM) showed a value of 6.21 × 103 s−1M−1. While the incubation of P. expansum spores with the purified lactonase did not inhibit spore germination, it inhibited colonization by the pathogen in apples. Furthermore, adding the purified enzyme to P. expansum culture before infecting apples resulted in reduced expression of genes involved in patulin biosynthesis and fungal cell wall biosynthesis. Some AHL-secreting bacteria also express AHL lactonase. Here, phylogenetic and structural analysis was used to identify putative lactonase in P. expansum. Furthermore, following recombinant expression and purification of the newly identified fungal enzyme, its activity with patulin was verified. These results indicate a possible role for patulin and lactonases in inter-kingdom communication between fungi and bacteria involved in fungal colonization and antagonism and suggest that QQ lactonases can be used as potential antifungal post-harvest treatment.

scholarly journals LitR of Vibrio salmonicida Is a Salinity-Sensitive Quorum-Sensing Regulator of Phenotypes Involved in Host Interactions and Virulence

2012 ◽  
Vol 80 (5) ◽  
pp. 1681-1689 ◽  
Author(s):  
Ane Mohn Bjelland ◽  
Henning Sørum ◽  
Daget Ayana Tegegne ◽  
Hanne C. Winther-Larsen ◽  
Nils Peder Willassen ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Cold Water ◽  
Bacterial Species ◽  
Cell Communication ◽  
Cell Aggregation ◽  
Fish Host ◽  
Content Type ◽  
Vibrio Salmonicida

ABSTRACTVibrio(Aliivibrio)salmonicidais the causal agent of cold-water vibriosis, a fatal bacterial septicemia primarily of farmed salmonid fish. The molecular mechanisms of invasion, colonization, and growth ofV. salmonicidain the host are still largely unknown, and few virulence factors have been identified. Quorum sensing (QS) is a cell-to-cell communication system known to regulate virulence and other activities in several bacterial species. The genome ofV. salmonicidaLFI1238 encodes products presumably involved in several QS systems. In this study, the gene encoding LitR, a homolog of the master regulator of QS inV. fischeri, was deleted. Compared to the parental strain, thelitRmutant showed increased motility, adhesion, cell-to-cell aggregation, and biofilm formation. Furthermore, thelitRmutant produced less cryptic bioluminescence, whereas production of acylhomoserine lactones was unaffected. Our results also indicate a salinity-sensitive regulation of LitR. Finally, reduced mortality was observed in Atlantic salmon infected with thelitRmutant, implying that the fish were more susceptible to infection with the wild type than with the mutant strain. We hypothesize that LitR inhibits biofilm formation and favors planktonic growth, with the latter being more adapted for pathogenesis in the fish host.

Quorum Sensing Regulation as a Target for Antimicrobial Therapy

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.

scholarly journals Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunrui Bo ◽  
Huixue Zhang ◽  
Yuze Cao ◽  
Xiaoyu Lu ◽  
Cong Zhang ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Mirna Gene ◽  
Experimental Studies ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Disease Genes ◽  
Feed Forward ◽  
Tf Gene

AbstractMyasthenia gravis (MG) is an autoimmune disease and the most common type of neuromuscular disease. Genes and miRNAs associated with MG have been widely studied; however, the molecular mechanisms of transcription factors (TFs) and the relationship among them remain unclear. A TF–miRNA–gene network (TMGN) of MG was constructed by extracting six regulatory pairs (TF–miRNA, miRNA–gene, TF–gene, miRNA–TF, gene–gene and miRNA–miRNA). Then, 3/4/5-node regulatory motifs were detected in the TMGN. Then, the motifs with the highest Z-score, occurring as 3/4/5-node composite feed-forward loops (FFLs), were selected as statistically significant motifs. By merging these motifs together, we constructed a 3/4/5-node composite FFL motif-specific subnetwork (CFMSN). Then, pathway and GO enrichment analyses were performed to further elucidate the mechanism of MG. In addition, the genes, TFs and miRNAs in the CFMSN were also utilized to identify potential drugs. Five related genes, 3 TFs and 13 miRNAs, were extracted from the CFMSN. As the most important TF in the CFMSN, MYC was inferred to play a critical role in MG. Pathway enrichment analysis showed that the genes and miRNAs in the CFMSN were mainly enriched in pathways related to cancer and infections. Furthermore, 21 drugs were identified through the CFMSN, of which estradiol, estramustine, raloxifene and tamoxifen have the potential to be novel drugs to treat MG. The present study provides MG-related TFs by constructing the CFMSN for further experimental studies and provides a novel perspective for new biomarkers and potential drugs for MG.

scholarly journals The vascular smooth muscle cell: a therapeutic target in Type 2 diabetes?

2013 ◽  
Vol 125 (4) ◽  
pp. 167-182 ◽  
Author(s):  
Karen E. Porter ◽  
Kirsten Riches
Keyword(s):  
Type 2 Diabetes ◽  
Smooth Muscle ◽  
Cardiovascular Risk ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Experimental Studies ◽  
Metabolic Memory ◽  
Diabetic Patients ◽  
Metabolic Disturbances

The rising epidemic of T2DM (Type 2 diabetes mellitus) worldwide is of significant concern. The inherently silent nature of the disease in its early stages precludes early detection; hence cardiovascular disease is often established by the time diabetes is diagnosed. This increased cardiovascular risk leads to significant morbidity and mortality in these individuals. Progressive development of complications as a result of previous exposure to metabolic disturbances appears to leave a long-lasting impression on cells of the vasculature that is not easily reversed and is termed ‘metabolic memory’. SMCs (smooth muscle cells) of blood vessel walls, through their inherent ability to switch between a contractile quiescent phenotype and an active secretory state, maintain vascular homoeostasis in health and development. This plasticity also confers SMCs with the essential capacity to adapt and remodel in pathological states. Emerging clinical and experimental studies propose that SMCs in diabetes may be functionally impaired and thus contribute to the increased incidence of macrovascular complications. Although this idea has general support, the underlying molecular mechanisms are currently unknown and hence are the subject of intense research. The aim of the present review is to explore and evaluate the current literature relating to the problem of vascular disease in T2DM and to discuss the critical role of SMCs in vascular remodelling. Possibilities for therapeutic strategies specifically at the level of T2DM SMCs, including recent novel advances in the areas of microRNAs and epigenetics, will be evaluated. Since restoring glucose control in diabetic patients has limited effect in ameliorating their cardiovascular risk, discovering alternative strategies that restrict or reverse disease progression is vital. Current research in this area will be discussed.

scholarly journals In-Silico Prediction and Modeling of the Quorum Sensing LuxS Protein and Inhibition of AI-2 Biosynthesis in Aeromonas hydrophila

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2627 ◽  
Author(s):  
Farman Ali ◽  
Zujie Yao ◽  
Wanxin Li ◽  
Lina Sun ◽  
Wenxiong Lin ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
In Silico ◽  
Bacterial Species ◽  
Critical Role ◽  
3D Structure ◽  
Docking Studies ◽  
Inhibition Mechanism ◽  
Inhibitor Molecule ◽  
Bioluminescence Assay ◽  
Luxs Protein

luxS is conserved in several bacterial species, including A. hydrophila, which causes infections in prawn, fish, and shrimp, and is consequently a great risk to the aquaculture industry and public health. luxS plays a critical role in the biosynthesis of the autoinducer-2 (AI-2), which performs wide-ranging functions in bacterial communication, and especially in quorum sensing (QS). The prediction of a 3D structure of the QS-associated LuxS protein is thus essential to better understand and control A. hydrophila pathogenecity. Here, we predicted the structure of A. hydrophila LuxS and characterized it structurally and functionally with in silico methods. The predicted structure of LuxS provides a framework to develop more complete structural and functional insights and will aid the mitigation of A. hydrophila infection, and the development of novel drugs to control infections. In addition to modeling, the suitable inhibitor was identified by high through put screening (HTS) against drug like subset of ZINC database and inhibitor ((−)-Dimethyl 2,3-O-isopropylidene-l-tartrate) molecule was selected based on the best drug score. Molecular docking studies were performed to find out the best binding affinity between LuxS homologous or predicted model of LuxS protein for the ligand selection. Remarkably, this inhibitor molecule establishes agreeable interfaces with amino acid residues LYS 23, VAL 35, ILE76, and SER 90, which are found to play an essential role in inhibition mechanism. These predictions were suggesting that the proposed inhibitor molecule may be considered as drug candidates against AI-2 biosynthesis of A. hydrophila. Therefore, (−)-Dimethyl 2,3-O-isopropylidene-l-tartrate inhibitor molecule was studied to confirm its potency of AI-2 biosynthesis inhibition. The results shows that the inhibitor molecule had a better efficacy in AI-2 inhibition at 40 μM concentration, which was further validated using Western blotting at a protein expression level. The AI-2 bioluminescence assay showed that the decreased amount of AI-2 biosynthesis and downregulation of LuxS protein play an important role in the AI-2 inhibition. Lastly, these experiments were conducted with the supplementation of antibiotics via cocktail therapy of AI-2 inhibitor plus OXY antibiotics, in order to determine the possibility of novel cocktail drug treatments of A. hydrophila infection.

scholarly journals Collective sensing and collective responses in quorum-sensing bacteria

2015 ◽  
Vol 12 (103) ◽  
pp. 20140882 ◽  
Author(s):  
R. Popat ◽  
D. M. Cornforth ◽  
L. McNally ◽  
S. P. Brown
Keyword(s):  
Quorum Sensing ◽  
Molecular Mechanisms ◽  
Environmental Parameters ◽  
Nutrient Concentrations ◽  
Environmental Challenges ◽  
Theoretical Approaches ◽  
Complex Decision Making ◽  
Evolution Of Resistance ◽  
Complex Decision ◽  
Antibacterial Chemotherapy

Bacteria often face fluctuating environments, and in response many species have evolved complex decision-making mechanisms to match their behaviour to the prevailing conditions. Some environmental cues provide direct and reliable information (such as nutrient concentrations) and can be responded to individually. Other environmental parameters are harder to infer and require a collective mechanism of sensing. In addition, some environmental challenges are best faced by a group of cells rather than an individual. In this review, we discuss how bacteria sense and overcome environmental challenges as a group using collective mechanisms of sensing, known as ‘quorum sensing’ (QS). QS is characterized by the release and detection of small molecules, potentially allowing individuals to infer environmental parameters such as density and mass transfer. While a great deal of the molecular mechanisms of QS have been described, there is still controversy over its functional role. We discuss what QS senses and how, what it controls and why, and how social dilemmas shape its evolution. Finally, there is a growing focus on the use of QS inhibitors as antibacterial chemotherapy. We discuss the claim that such a strategy could overcome the evolution of resistance. By linking existing theoretical approaches to data, we hope this review will spur greater collaboration between experimental and theoretical researchers.

scholarly journals A molecular model of the surface-assisted protein aggregation process

2018 ◽  
Author(s):  
Y.G. Pan ◽  
S. Banerjee ◽  
K. Zagorski ◽  
L.S. Shlyakhtenko ◽  
A.B. Kolomeisky ◽  
...  
Keyword(s):  
Self Assembly ◽  
Molecular Mechanisms ◽  
Molecular Model ◽  
Critical Role ◽  
Experimental Studies ◽  
Cytosine Deaminase ◽  
Aggregation Process ◽  
Amyloidogenic Proteins ◽  
Low Concentrations ◽  
Kinetics Of

AbstractThe importance of cell surfaces in the self-assembly of proteins is widely accepted. One biologically significant event is the assembly of amyloidogenic proteins into aggregates, which leads to neurodegenerative disorders like Alzheimer’s and Parkinson’s. The interaction of amyloidogenic proteins with cellular membranes appears to dramatically facilitate the aggregation process. Recent findings indicate that, in the presence of surfaces, aggregation occurs at physiologically low concentrations, suggesting interaction with surfaces plays a critical role in the disease-prone aggregation process. However, the molecular mechanisms behind on-surface aggregation remain unclear. Here we provide a theoretical model that offers a molecular explanation. According to this model, monomers transiently immobilized to surfaces increase the local monomer protein concentration and thus work as nuclei to dramatically accelerate the entire aggregation process. This theory was verified by experimental studies, using mica surfaces, to examine the aggregation kinetics of amyloidogenic-synuclein protein (α-Syn) and non-amyloidogenic cytosine deaminase APOBEC3G (A3G).

The capacity of short term memory from an evolutionary perspective

2019 ◽  
Author(s):  
Majid Manoochehri
Keyword(s):  
Short Term Memory ◽  
Memory Span ◽  
Critical Role ◽  
Experimental Studies ◽  
Cognitive System ◽  
Evolutionary Approach ◽  
Evolutionary Perspective ◽  
Short Term ◽  
Term Memory

Memory span in humans has been intensely studied for more than a century. In spite of the critical role of memory span in our cognitive system, which intensifies the importance of fundamental determinants of its evolution, few studies have investigated it by taking an evolutionary approach. Overall, we know hardly anything about the evolution of memory components. In the present study, I briefly review the experimental studies of memory span in humans and non-human animals and shortly discuss some of the relevant evolutionary hypotheses.

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