Characterization of cooperators in Quorum sensing with 2D molecular signal analysis

In quorum sensing (QS), bacteria exchange molecular signals to work together. An analytically-tractable model is presented for characterizing QS signal propagation within a population of bacteria and the number of responsive cooperative bacteria (i.e., cooperators) in a two-dimensional (2D) environment. Unlike prior works with a deterministic topology and a simplified molecular propagation channel, this work considers continuous emission, diffusion, degradation, and reception among randomly-distributed bacteria. Using stochastic geometry, the 2D channel response and the corresponding probability of cooperation at a bacterium are derived. Based on this probability, new expressions are derived for the moment generating function and different orders of moments of the number of cooperators. The analytical results agree with the simulation results obtained by a particle-based method. In addition, the Poisson and Gaussian distributions are compared to approximate the distribution of the number of cooperators and the Poisson distribution provides the best overall approximation. The derived channel response can be generally applied to any molecular communication model where single or multiple transmitters continuously release molecules into a 2D environment. The derived statistics of the number of cooperators can be used to predict and control the QS process, e.g., predicting and decreasing the likelihood of biofilm formation

Maintenance of Microbial Cooperation Mediated by Public Goods in Single- and Multiple-Trait Scenarios

Microbes often form densely populated communities, which favor competitive and cooperative interactions. Cooperation among bacteria often occurs through the production of metabolically costly molecules produced by certain individuals that become available to other neighboring individuals; such molecules are called public goods. This type of cooperation is susceptible to exploitation, since nonproducers of a public good can benefit from it while saving the cost of its production (cheating), gaining a fitness advantage over producers (cooperators). Thus, in mixed cultures, cheaters can increase in frequency in the population, relative to cooperators. Sometimes, and as predicted by simple game-theoretic arguments, such increases in the frequency of cheaters cause loss of the cooperative traits by exhaustion of the public goods, eventually leading to a collapse of the entire population. In other cases, however, both cooperators and cheaters remain in coexistence. This raises the question of how cooperation is maintained in microbial populations. Several strategies to prevent cheating have been studied in the context of a single trait and a unique environmental constraint. In this review, we describe current knowledge on the evolutionary stability of microbial cooperation and discuss recent discoveries describing the mechanisms operating in multiple-trait and multiple-constraint settings. We conclude with a consideration of the consequences of these complex interactions, and we briefly discuss the potential role of social interactions involving multiple traits and multiple environmental constraints in the evolution of specialization and division of labor in microbes.info:eu-repo/semantics/publishedVersio

Lubricating Bacteria Model for Branching growth of Bacterial Colonies

Various bacterial strains (e.g. strains belonging to the genera Bacillus, Paenibacillus, Serratia and Salmonella) exhibit colonial branching patterns during growth on poor semi-solid substrates. These patterns reflect the bacterial cooperative self-organization. Central part of the cooperation is the collective formation of lubricant on top of the agar which enables the bacteria to swim. Hence it provides the colony means to advance towards the food. One method of modeling the colonial development is via coupled reaction-diffusion equations which describe the time evolution of the bacterial density and the concentrations of the relevant chemical fields. This idea has been pursued by a number of groups. Here we present an additional model which specifically includes an evolution equation for the lubricant excreted by the bacteria. We show that when the diffusion of the fluid is governed by nonlinear diffusion coefficient branching patterns evolves. We study the effect of the rates of emission and decomposition of the lubricant fluid on the observed patterns. The results are compared with experimental observations. We also include fields of chemotactic agents and food chemotaxis and conclude that these features are needed in order to explain the observations.Comment: 1 latex file, 16 jpeg files, submitted to Phys. Rev.

Studies of Bacterial Branching Growth using Reaction-Diffusion Models for Colonial Development

Various bacterial strains exhibit colonial branching patterns during growth on poor substrates. These patterns reflect bacterial cooperative self-organization and cybernetic processes of communication, regulation and control employed during colonial development. One method of modeling is the continuous, or coupled reaction-diffusion approach, in which continuous time evolution equations describe the bacterial density and the concentration of the relevant chemical fields. In the context of branching growth, this idea has been pursued by a number of groups. We present an additional model which includes a lubrication fluid excreted by the bacteria. We also add fields of chemotactic agents to the other models. We then present a critique of this whole enterprise with focus on the models' potential for revealing new biological features.Comment: 1 latex file, 40 gif/jpeg files (compressed into tar-gzip). Physica A, in pres

Quorum sensing dynamics in the alpha-proteobacterium Sinorhizobium meliloti at the single-cell and population level

In quorum sensing, bacteria produce and release so-called autoinducers that accumulate in the environment while the cells grow. Once these molecules reach a threshold concentration, they trigger major behavioral changes in the population. Since the triggered behaviors are thought to be effective only when performed by a large enough group, autoinducers are generally taken to indicate when this sufficient cell density has been reached. However, little is known about how these components interact dynamically at the single-cell level to fulfill their task of cell-cell communication. Furthermore, quorum sensing is often studied in well-shaken liquid cultures, but little is known about autoinducer dispersal and response dynamics over larger distances in physiological niches like the rhizosphere where active mixing is negligible. The aim of this work therefore was to investigate these aspects in the model organism Sinorhizobium meliloti. In (Bettenworth et al., 2022.), quorum sensing dynamics were investigated with respect to autoinducer synthase gene expression in single cells and the timing of the response in the respective colonies. Surprisingly, in S. meliloti the autoinducer synthase gene is not expressed continuously, but in discrete stochastic pulses. Stochasticity stems from scarcity and, presumably, low binding affinity of the essential transcription activator. Physiological factors modulate abundance of this activator or its binding affinity to the autoinducer synthase gene promoter and thereby modulate gene expression pulse frequency. Higher or lower pulse frequencies in turn trigger the onset of the quorum sensing response at lower or higher cell numbers, respectively. In other words: S. meliloti quorum sensing is based on a stochastic regulatory system that encodes each cell’s physiological condition in the pulse frequency with which it expresses its autoinducer synthase gene; pulse frequencies of all members of a population are then integrated in the common pool of autoinducers. Only once this vote crosses the threshold, the response behavior is initiated. Consequently, S. meliloti quorum sensing is not so much a matter of counting cell numbers as suggested by the analogy of the quorum, but more comparable to a voting in a local community, or the collective decision-making described for social insects (Bettenworth et al., 2022). In (Bettenworth et al., 2018), the dynamics of autoinducer dispersal by diffusion in a two-dimensional environment were explored. At first sight, diffusive spreading should yield a dilution of the molecules and, with increasing distance from the source, slow down progression of the concentration level necessary to trigger a response in distantly located receiver cells. In contrast to this expectation, however, this threshold concentration did not decelerate in respective experiments, but instead travelled with constant speed, comparable to front propagation in pattern-forming systems. According to a mathematical model, this effect was due to the exponential growth of the sender cells which yielded adding-up of an exponentially growing number of autoinducer concentration profiles, thus compensating for the thinning effect of diffusion. Consequently, even a single sender colony could induce a response in receiver cells up to 7 mm away (Bettenworth et al., 2018)

A simple model for the early events of quorum sensing in Pseudomonas aeruginosa: modeling bacterial swarming as the movement of an "activation zone"

<p>Abstract</p> <p>Background</p> <p>Quorum sensing (QS) is a form of gene regulation based on cell-density that depends on inter-cellular communication. While there are a variety of models for bacterial colony morphology, there is little work linking QS genes to movement in an open system.</p> <p>Results</p> <p>The onset of swarming in environmental <it>P. aeruginosa </it>PUPa3 was described with a simplified computational model in which cells in random motion communicate via a diffusible signal (representing <it>N</it>-acyl homoserine lactones, AHL) as well as diffusible, secreted factors (enzymes, biosurfactans, i.e. "public goods") that regulate the intensity of movement and metabolism in a threshold-dependent manner. As a result, an "activation zone" emerges in which nutrients and other public goods are present in sufficient quantities, and swarming is the spontaneous displacement of this high cell-density zone towards nutrients and/or exogenous signals. The model correctly predicts the behaviour of genomic knockout mutants in which the QS genes responsible either for the synthesis (<it>lasI, rhlI</it>) or the sensing (<it>lasR, rhlR</it>) of AHL signals were inactivated. For wild type cells the model predicts sustained colony growth that can however be collapsed by the overconsumption of nutrients.</p> <p>Conclusion</p> <p>While in more complex models include self-orienting abilities that allow cells to follow concentration gradients of nutrients and chemotactic agents, in this model, displacement towards nutrients or environmental signals is an emergent property of the community that results from the action of a few, well-defined QS genes and their products. Still the model qualitatively describes the salient properties of QS bacteria, i.e. the density-dependent onset of swarming as well as the response to exogenous signals or cues.</p> <p>Reviewers</p> <p>This paper was reviewed by Gáspár Jékely, L. Aravind, Eugene V. Koonin and Artem Novozhilov (nominated by Eugene V. Koonin).</p

Cooperative signal amplification for molecular communication in nanonetworks.

English: Nanotechnology is enabling the development of devices in a scale ranging from a few to hundreds of nanometers. Communication between these devices greatly expands the possible applications, increasing the complexity and range of operation of the system. In particular, the resulting nanocommunication networks (or nanonetworks) show great potential for applications in the biomedical field, in which diffusion-based molecular communication is regarded as a promising alternative to electromagnetic-based solutions due to the bio-stability and energy-related requirements of this scenario. In this new paradigm, the information is encoded into pulses of molecules that reach the receiver by means of diffusion. However, molecular signals suffer a significant amount of attenuation as they propagate through the medium, thus limiting the transmission range. In this work we propose, among others, a signal amplification scheme for molecular communication nanonetworks in which a group of emitters jointly transmits a given signal after achieving synchronization by means of Quorum Sensing. By using the proposed methodology, the transmission range is extended proportionally to the number of synchronized emitters. We also provide an analytical model of Quorum Sensing, validated through simulation. This model accounts for the activation threshold (which will eventually determine the resulting amplification level) and the delay of the synchronization process.Castellano: La nanotecnología permite el desarrollo de dispositivos en una escala que va de las unidades a centenares de nanómetros. La comunicación entre estos dispositivos hace aumentar el número de aplicaciones posibles, ya que se mejora la complejidad y el rango de actuación del sistema. En concreto, las redes de nanocomunicaciones (o nanoredes) resultantes muestran un gran potencial cuando se trata de aplicaciones biomédicas, en las cuales la comunicación molecular basada en difusión de partículas supera a las soluciones electromagnéticas clásicas debido a las imposiciones energéticas y de biocompatibilidad de este escenario. En este nuevo paradigma de comunicación, la información se codifica en pulsos de moléculas que llegan al receptor gracias al fenómeno de la difusión. No obstante, las señales moleculares son sometidas a una gran atenuación a medida que se propagan a través del medio, hecho que limita severamente el alcance o rango de transmisión. En esta tesis se propone, entre otros, un esquema de amplificación de la señal para nanoredes de comunicación molecular, en el cual un grupo de emisores transmite una cierta señal de manera conjunta después de haberse sincronizado mediante la ejecución de Quorum Sensing. Con el método que proponemos, el alcance aumenta proporcionalmente al número de transmisores que se sincronizan. Además, proponemos un modelo analítico de Quorum Sensing, el cual se valida mediante simulación. Dicho modelo permite calcular el nivel umbral de activación del conjunto (hecho que determina la amplificación resultante y el rango de transmisión final) y el retardo que el proceso de sincronización introduce.Català: La nanotecnologia permet el desenvolupament de dispositius en una escala de unitats a centenars de nanòmetres. La comunicació entre aquests dispositius fa augmentar el nombre de possibles aplicacions, ja que es millora la complexitat i el rang d'actuació del sistema. En concret, les xarxes de nanocomunicacions (o nanoxarxes) resultants mostren un gran potencial quan ens referim a aplicacions biomèdiques, en les quals la comunicació molecular basada en difusió de partícules supera a les solucions de caire electromagnètic degut a les imposicions energètiques i de biocompatilitat d'aquest escenari. En aquest nou paradigma de comunicació, la informació és codificada en polsos de molècules que arriben al receptor gràcies al fenomen de la difusió. No obstant, els senyals moleculars són sotmesos a una gran atenuació a mesura que es propaguen a través del medi, fet que limita severament el rang de transmissió. En aquesta tesi es proposa, entre d'altres, un esquema d'amplificació del senyal per a nanoxarxes de comunicació molecular, en el qual un grup d'emissors transmet un cert senyal de manera conjunta després d'haver-se sincronitzat executant Quorum Sensing. Amb el mètode que proposem, l'abast o rang de transmissió augmenta proporcionalment al nombre d'emissors que se sincronitzen. A més a més, proposem un model analític de Quorum Sensing, el qual és validat mitjançant simulació. Dit model permet calcular el nivell llindar d'activació del conjunt (que de fet determina l'amplificació resultant i el rang de transmissió final) i el retard que el procés de sincronització introdueix