Quorum sensing: a quantum perspective

Quorum sensing is the efficient mode of communication in the bacterial world. After a lot of advancements in the classical theory of quorum sensing few basic questions of quorum sensing still remain unanswered. The sufficient progresses in quantum biology demands to explain these questions from the quantum perspective as non trivial quantum effects already have manifested in various biological processes like photosynthesis, magneto-reception etc. Therefore, it’s the time to review the bacterial communications from the quantum view point. In this article we carefully accumulate the latest results and arguments to strengthen quantum biology through the addition of quorum sensing mechanism in the light of quantum mechanics.     

Applications of quorum sensing in biotechnology

Many unicellular microorganisms use small signaling molecules to determine their local concentration. The processes involved in the production and recognition of these signals are collectively known as quorum sensing (QS). This form of cell–cell communication is used by unicellular microorganisms to co-ordinate their activities, which allows them to function as multi-cellular systems. Recently, several groups have demonstrated artificial intra-species and inter-species communication through synthetic circuits which incorporate components of bacterial QS systems. Engineered QS-based circuits have a wide range of applications such as production of biochemicals, tissue engineering, and mixed-species fermentations. They are also highly useful in designing microbial biosensors to identify bacterial species present in the environment and within living organisms. In this review, we first provide an overview of bacterial QS systems and the mechanisms developed by bacteria and higher organisms to obstruct QS communications. Next, we describe the different ways in which researchers have designed QS-based circuits and their applications in biotechnology. Finally, disruption of quorum sensing is discussed as a viable strategy for preventing the formation of harmful biofilms in membrane bioreactors and marine transportation.     

Extracellular noise-induced stochastic synchronization in heterogeneous quorum sensing network

Quorum sensing is a bacterial mechanism used to synchronize the coordinated response of a microbial population. Because quorum sensing in Gram-negative bacteria depends on release and detection of a diffusible signaling molecule (autoinducer) among a multicellular group, it is considered a simple form of cell-cell communication for the purposes of mathematical analysis. Stochastic equation systems have provided a common approach to model biochemical or biophysical processes. Recently, the effect of noise to synchronize a specific homogeneous quorum sensing network was successfully modeled using a stochastic equation system with fixed parameters. The question remains of how to model quorum sensing networks in a general setting. To address this question, we first set a stochastic equation system as a general model for a heterogeneous quorum sensing network. Then, using two relevant biophysical characteristics of Gram-negative bacteria (the permeability of the cell membrane to the autoinducer and the symmetry of autoinducer diffusion) we construct the solution of the stochastic equation system at an abstract level. The solution indicates that stable synchronization of a quorum sensing network is robustly induced by an environment with a heterogenous distribution of extracellular and intracellular noise. The synchronization is independent of the initial state of the system and is solely the result of the connectivity of the cell network established through the effects of extracellular noise.     

Quorum signaling via AI-2 communicates the "Metabolic Burden" associated with heterologous protein production in Escherichia coli.

Recent reports have shown that bacterial cell-cell communication or quorum sensing is quite prevalent in pathogenic Escherichia coli, especially at high cell density; however, the role of quorum sensing in nonpathogenic E. coli is less clear and, in particular, there is no information regarding the role of quorum sensing in overexpression of plasmid-encoded genes. In this work, it was found that the activity of a quorum signaling molecule, autoinducer-2 (AI-2), decreased significantly following induction of several plasmid-encoded genes in both low and high-cell-density cultures of E. coli. Furthermore, we show that AI-2 signaling level was linearly related to the accumulation level of each protein product and that, in general, the highest rates of recombinant protein accumulation resulted in the greatest attenuation of AI-2 signaling. Importantly, our findings demonstrate for the first time that recombinant E. coli communicate the stress or burden of overexpressing heterologous genes through the quorum-based AI-2 signaling pathway.     

群体感应与微生物耐药性

微生物耐药性已成为全球关注的严重问题,其演化机制和调控机理也已成为研究热点。近年来的研究发现,一些微生物耐药性机制受到群体感应系统的调控。群体感应是一种在微生物界广泛存在并与菌体密度关联的细胞-细胞间的通讯系统。高密度的菌落群体能够产生足够数量的小分子信号,激活下游包括致病毒力和耐药性机制在内的多种细胞进程,耐受抗生素并且危害寄主。本文结合国内外最新的研究进展,对微生物群体感应系统的研究现状进行了概括性介绍,重点阐述了群体感应系统对微生物耐药性机制的调控作用,如微生物生物被膜形成和药物外排泵调控等方面的作用,并探讨了利用群体淬灭控制微生物耐药性的新策略。     

Quorum sensing intervened bacterial signaling: Pursuit of its cognizance and repression

Bacteria communicate within a system by means of a density dependent mechanism known as quorum sensing which regulate the metabolic and behavioral activities of a bacterial community. This sort of interaction occurs through a dialect of chemical signals called as autoinducers synthesized by bacteria. Bacterial quorum sensing occurs through various complex pathways depending upon specious diversity. Therefore the cognizance of quorum sensing mechanism will enable the regulation and thereby constrain bacterial communication. Inhibition strategies of quorum sensing are collectively called as quorum quenching; through which bacteria are incapacitated of its interaction with each other. Many virulence mechanism such as sporulation, biofilm formation, toxin production can be blocked by quorum quenching. Usually quorum quenching mechanisms can be broadly classified into enzymatic methods and non-enzymatic methods. Substantial understanding of bacterial communication and its inhibition enhances the development of novel antibacterial therapeutic drugs. In this review we have discussed the types and mechanisms of quorum sensing and various methods to inhibit and regulate density dependent bacterial communication.     

Modeling of Cell-to-Cell Communication Processes with Petri Nets Using the Example of Quorum Sensing

The understanding of the molecular mechanism of cell-to-cell communication is fundamental for system biology. Up to now, the main objectives of bioinformatics have been reconstruction, modeling and analysis of metabolic, regulatory and signaling processes, based on data generated from high-throughput technologies. Cell-to-cell communication or quorum sensing (QS), the use of small molecule signals to coordinate complex patterns of behavior in bacteria, has been the focus of many reports over the past decade. Based on the quorum sensing process of the organism Aliivibrio salmonicida, we aim at developing a functional Petri net, which will allow modeling and simulating cell-to-cell communication processes. Using a new editor-controlled information system called VANESA (http://vanesa.sf.net), we present how to combine different fields of studies such as life-science, database consulting, modeling, visualization and simulation for a semi-automatic reconstruction of the complex signaling quorum sensing network. We show how cell-to-cell communication processes and information-flow within a cell and across cell colonies can be modeled using VANESA and how those models can be simulated with Petri net network structures in a sophisticated way.     

Electrogenetic signaling and information propagation for controlling microbial consortia via programmed lysis

To probe signal propagation and genetic actuation in microbial consortia, we have coopted the components of both redox and quorum sensing (QS) signaling into a communication network for guiding composition by “programming” cell lysis. Here, we use an electrode to generate hydrogen peroxide as a redox cue that determines consortia composition. The oxidative stress regulon of Escherichia coli, OxyR, is employed to receive and transform this signal into a QS signal that coordinates the lysis of a subpopulation of cells. We examine a suite of information transfer modalities including “monoculture” and “transmitter-receiver” models, as well as a series of genetic circuits that introduce time-delays for altering information relay, thereby expanding design space. A simple mathematical model aids in developing communication schemes that accommodate the transient nature of redox signals and the “collective” attributes of QS signals. We suggest this platform methodology will be useful in understanding and controlling synthetic microbial consortia for a variety of applications, including biomanufacturing and biocontainment.     

微生物的交流信号

多年来微生物一直被认为是相对孤立的个体,在环境中独立地生存,但近些年的研究使人们认识到微生物也使用复杂多样的方式进行种内、种间,甚至与其他生物间的跨界信息交流。这些交流由特定的信号分子来完成,称之为微生物语言。借助这些交流语言使微生物在特定的生态位中与其相邻个体或种群建立了多样的互动关系,包括合作、竞争与资源共享等,通过协调群体行为,共同应对多变的环境。随着现代分子科学对自然微生物群落的不断深入研究,人们对微生物交流也逐渐有了更为清晰的认知。本综述总结了原核和真核微生物所使用的主要信号物质(如群体感应、群体猝灭、抗生素等)和交流方式,讨论了这些通讯语言在种内(同种微生物)、种间(异种微生物),以及跨界(微生物与宿主)交流上的表现。旨在更为深入地解读这一有趣的多学科交叉研究领域,更好地理解微生物交流语言的形式、机制和目的,为微生物行为的解读和生态事件的解析获取基于化学生态学的新思路。     

Cross- species communication in bacterial world

Biofilms are the compact association of micro organisms and the communication processes in these biofilms are always a wonder. Electrical and chemical signaling mechanism are the key to understand the bacterial communication network. Quorum sensing so far has been able to explain the coordinated motion of bacteria through its chemical signaling mechanism. Bacteria residing within biofilm communities are trivial to communicate. But the recent observation in 2017 by Humphries et al. has revealed that the ion channels enabled electrical signaling mechanism can be as powerful as to attract the distant cells i.e., this signaling mechanism are capable of holding a long range behavior. As a result long range cross species communication in the bacterial world have been possible. This substantial outcome has brought this field into a new paradigm to investigate the complex co-existence of biofilm communities and distant cells with a possible scope of application in synthetic biology. In this present article, we briefly describe this new signaling mechanism and how it gives rise to a long range communication ability in bacterial communities.     

海洋微生物群体感应与群体感应淬灭的开发利用

群体感应与感应淬灭在微生物中普遍存在,群体感应通过调控基因表达赋予细菌有益或有害的特性,这些特性与人类健康、农业及水产养殖等领域密切相关。群体感应现象首先发现于海洋环境,近几年海洋采样等相关技术的发展,极大促进了海洋微生物的群体感应与淬灭研究的快速发展。本文对细菌及典型真菌的群体感应作用机制、信号分子的多样性以及其与细菌致病性的相关性进行了阐述,对群体感应淬灭的机制与意义、淬灭因子多样性以及相关酶资源的发掘也进行了分析和展望。     

细菌群体感应“合作-欺骗”研究进展

细菌利用信号分子进行细胞间的交流即为群体感应.群体感应调控着生物膜形成、公共物质合成、基因水平转移等一系列社会性行为.在群体感应过程中,公共物质分泌后可以被群体中任何个体所使用即合作;亦可以被一些不分泌公共物质的个体所使用形成欺骗.群体感应合作-欺骗既可能在种群中稳定维持,也可能由于欺骗子的快速增长造成种群崩溃.欺骗子致种群崩溃为病原菌控制新策略研发带来了希望,是目前群体感应研究方面的前沿和热点.本文在介绍细菌群体感应合作及欺骗的基础上,分析了群体感应合作-欺骗生态关系形成和发展的影响因素,重点从亲缘选择、谨慎代谢、代谢限制(基因多效型)、群体感应监管等方面探讨了细菌群体感应合作-欺骗的稳定维持机制,并对细菌群体感应合作-欺骗的相关研究进行了问题总结和展望,以期为深入理解群体感应、微生物种群生态提供参考.     

群体感应在生物强化功能菌定殖及降解能力增强中的作用研究进展

由于难降解有机污染物和外界环境对水处理系统的冲击干扰,污水水质常出现不达标现象。引入外源含有相关功能基因并且具有基因水平转移能力的工程菌株进行生物强化处理是提高污水处理效能的有效措施。污水处理系统中存在能够分泌信号分子的菌体,菌间具有群体感应现象,当种群密度达到感应阈值时,菌体会通过释放信号分子来触发一些群体行为,从而激活相关基因的表达(如生物膜形成、生物发光、抗生素合成和毒力因子表达等)。早期的群体感应技术研究主要集中在信号传递学、微生物社会行为学和医学微生物领域,近年来,在水处理领域也开始有相继报道,研究表明群体感应在污水生物处理中发挥重要作用,并且影响生物强化菌株的定殖和污染物降解,因此群体感应行为调控是生物强化技术成效显著与否的关键因素。本文综述了群体感应及信号分子的作用机制、信号分子释放及存在的影响因素以及群体感应对菌株定殖、微生物群落结构和污染物去除的影响,并对从群体感应角度出发研究生物强化过程进行了展望,旨在为生物强化技术的有效实施及提升污水处理效能提供一种新思路,为深入理解生物强化过程中群体感应调控行为提供理论参考。     

A Social Medium: ASM's 5th Cell-Cell Communication in Bacteria Meeting in Review

The 5th American Society for Microbiology Conference on Cell-Cell Communication in Bacteria (CCCB-5), which convened from 18 to 21 October 2014 in San Antonio, TX, highlighted recent advances in our understanding of microbial intercellular signaling. While the CCCB meetings arose from interests in pheromone signaling and quorum sensing, it was evident at CCCB-5 that the cell-cell communication field is continuing to mature, expanding into new areas and integrating cutting-edge technologies. In this minireview, we recap some of the research discussed at CCCB-5 and the questions that have arisen from it.     

LuxS quorum sensing: more than just a numbers game

Quorum sensing is a process of bacterial cell-to-cell communication involving the production and detection of extracellular signaling molecules called autoinducers. Quorum sensing allows populations of bacteria to collectively control gene expression, and thus synchronize group behavior. Processes controlled by quorum sensing are typically ones that are unproductive unless many bacteria act together. Most autoinducers enable intraspecies communication; however, a recently discovered autoinducer AI-2 has been proposed to serve as a 'universal signal' for interspecies communication. Studies suggest that AI-2 encodes information in addition to specifics about cell number.     

Stochastic simulations of a synthetic bacteria-yeast ecosystem

ABSTRACT: BACKGROUND: The eld of synthetic biology has greatly evolved and numerous functions can now be implemented by articially engineered cells carrying the appropriate genetic information. However, in order for the cells to robustly perform complex or multiple tasks, co-operation between them may be necessary. Therefore, various synthetic biological systems whose functionality requires cell-cell communication are being designed. These systems, microbial consortia, are composed of engineered cells and exhibit a wide range of behaviors. These include yeast cells whose growth is dependent on one another, or bacteria that kill or rescue each other, synchronize, behave as predator-prey ecosystems or invade cancer cells. RESULTS: In this paper, we study a synthetic ecosystem comprising of bacteria and yeast that communicate with and benet from each other using small diffusible molecules. We explore the behavior of this heterogeneous microbial consortium, composed of Saccharomyces cerevisiae and Escherichia coli cells, using stochastic modeling. The stochastic model captures the relevant intra-cellular and inter-cellular interactions taking place in and between the eukaryotic and prokaryotic cells. Integration of well-characterized molecular regulatory elements into these two microbes allows for communication through quorum sensing. A gene controlling growth in yeast is induced by bacteria via chemical signals and vice versa. Interesting dynamics that are common in natural ecosystems, such as obligatory and facultative mutualism, extinction, commensalism and predator-prey like dynamics are observed. We investigate and report on the conditions under which the two species can successfully communicate and rescue each other. CONCLUSIONS: This study explores the various behaviors exhibited by the cohabitation of engineered yeast and bacterial cells. The way that the model is built allows for studying the dynamics of any system consisting of two species communicating with one another via chemical signals. Therefore, key information acquired by our model may potentially drive the experimental design of various synthetic heterogeneous ecosystems.     

废水处理中群体感应调控行为研究进展

群体感应是微生物在繁殖过程中分泌一些特定的信号分子,当信号分子浓度达到一定阈值后,可以调控某些基因表达,从而实现信息交流的现象.群体感应调控着生物膜形成、公共物质合成、基因水平转移等一系列社会性行为,广泛存在于各类微生物信息交流中.活性污泥、生物膜和颗粒污泥等生物聚集体广泛存在群体感应现象,了解和认识群体感应与微生物之间的调控行为,对于废水处理具有重要意义.本文综述了感应信号分子的分类、群体感应调控机制,群体感应在活性污泥、生物膜、好氧颗粒污泥和厌氧颗粒污泥等废水处理中的调控行为的研究进展,并对废水处理中群体感应的研究进行了展望,以期为深入理解废水处理中群体感应调控行为提供参考.     

外源基因表达造成的群体感应细菌生存压力的建模分析

外源基因的表达及其对细菌种群的影响对于群体感应系统和合成生物学产业的研究具有重要意义。然而,人们对于表达外源蛋白的细菌本身的行为模式仍然知之甚少。为了研究菌落生长和外源基因表达的过程究竟受到哪些因素的影响,文中测量了受Lux类受体调控的外源基因在N-酰基高丝氨酸内酯 (N-acyl homoserine lactone,N-AHL) 信号分子诱导下的表达,并模拟了其对细菌种群动态的影响。文中建立了一个假设性的数学模型,对信号分子诱导表达下细菌种群生长受影响的现象进行了分析。先前的研究通常将细菌种群生长受群体感应系统影响的现象归咎于合成群体感应信号分子的消耗与N-AHL信号分子的毒性,文中提供了对于这种生存压力的另一种可能的解释。     

Monitoring of Vibrio harveyi quorum sensing activity in real time during infection of brine shrimp larvae

Quorum sensing, bacterial cell-to-cell communication, has been linked to the virulence of pathogenic bacteria. Indeed, in vitro experiments have shown that many bacterial pathogens regulate the expression of virulence genes by this cell-to-cell communication process. Moreover, signal molecules have been detected in samples retrieved from infected hosts and quorum sensing disruption has been reported to result in reduced virulence in different host–pathogen systems. However, data on in vivo quorum sensing activity of pathogens during infection of a host are currently lacking. We previously reported that quorum sensing regulates the virulence of Vibrio harveyi in a standardised model system with gnotobiotic brine shrimp (Artemia franciscana) larvae. Here, we monitored quorum sensing activity in Vibrio harveyi during infection of the shrimp, using bioluminescence as a read-out. We found that wild-type Vibrio harveyi shows a strong increase in quorum sensing activity early during infection. In this respect, the bacteria behave remarkably similar in different larvae, despite the fact that only half of them survive the infection. Interestingly, when expressed per bacterial cell, Vibrio harveyi showed around 200-fold higher maximal quorum sensing-regulated bioluminescence when associated with larvae than in the culture water. Finally, the in vivo quorum sensing activity of mutants defective in the production of one of the three signal molecules is consistent with their virulence, with no detectable in vivo quorum sensing activity in AI-2- and CAI-1-deficient mutants. These results indicate that AI-2 and CAI-1 are the dominant signals during infection of brine shrimp.