群体感应QseB/QseC系统对外界环境变化的响应机制

细菌群体感应(quorum sensing, QS)是一种细菌种群之间和与环境之间的相互作用机制，不仅可以评估其自身物种的种群密度，还可以评估给定环境中其他细菌物种的种群密度，是维持细菌感知并响应环境变化的重要协调途径。编码鞭毛表达和组装以及运动性的基因是潜在的毒力相关因子，受细菌种群密度调节，利用群体感应激活。QseB/QseC双组分系统是参与鞭毛和运动基因调节的群体感应调节级联反应的一个重要组成部分。本文综述了细菌群体感应系统的种类及其作用，将近年来有关QseB/QseC双组分系统介导的群体感应系统结构功能、QseB/QseC信号转导调控机制以及QseB/QseC双组分系统在调控细菌致病性、生物膜形成、鞭毛运动性等方面所发挥的作用进行整理、归纳和总结，并对目前研究不足的地方作出了展望，希望能找出下一个研究的方向。对QseB/QseC信号系统介导的群体感应机制的深入研究，不仅为解决细菌耐药及致病机制等问题提供新思路，还可能为开发疫苗和药物提供新靶点。     

细菌群体感应调控多样性及群体感应淬灭

群体感应(Quorum sensing, QS)是细菌通过信号分子分泌、识别,从而调控基因水平转移、毒力因子分泌、芽孢产生及生物膜形成等群体行为的细胞交流机制。干扰信号分子的分泌、识别,可以阻断群体感应,实现群体淬灭。群体淬灭(Quorum quenching, QQ)是目前致病性控制、致腐性预防以及生物膜污染削减的重要策略之一。本文以群体感应信号分泌-识别-响应为主线,将群体感应分为等级、平行及竞争型三类调控方式,并对其特征进行了详细阐述;同时,探讨了信号分子类似物、信号分子降解酶剂、信号受体激活剂/抑制剂等策略在不同调控方式淬灭中的适用性;最后,对群体感应调控及淬灭进行了展望,以期为丰富细菌群体感应认知、促进群体淬灭应用提供参考。     

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.     

海绵共栖细菌NJ6-3-1基于群体感应调控的抗菌活性

[目的]选择一株海绵共栖细菌Pseudoalteromonas sp.NJ6-3-1,研究其抗菌物质的代谢是否受到群体感应的调控.[方法]我们研究了在不同生长条件细菌NJ6-3-1代谢物的抗菌活性与细胞密度的关系;通过模拟自然的竞争环境,研究了低密度条件下的细菌NJ6-3-1与外源细菌Staphylococcus aureus共培养时的抗菌活性情况.[结果]实验发现细菌NJ6-3-1代谢抗菌物质的行为与细胞密度密切相关,只有当细胞密度达到一定的阈值OD630=0.4时,NJ6-3-1才能代谢抗菌物质;同时发现外源病原菌S.aureus代谢产物中存在某种信号分子,能诱导NJ6-3-1在不产生抗菌物质的生长条件下代谢抗菌物质.[结论]以上结果初步说明NJ6-3-1的抗菌活性受到种内和种间群体感应系统的调控.     

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。     

外源基因表达造成的群体感应细菌生存压力的建模分析（英文）

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。     

海洋微生物群体感应抑制剂研究进展

海洋生态环境复杂多变,其未被开发的栖息地蕴藏着丰富且稀有的生物资源,具有高盐、高压、寡营养、常年高温或低温等特点。海洋微生物经过长期持续的缓慢进化,已形成独特的代谢机制来适应海洋相对特殊的生态环境,极大地增加了发现新型活性物质的可能性。因此,海洋微生物代谢产物被认为是发现新型天然活性化合物(群体感应抑制剂)的潜在来源。本文首先介绍群体感应概念及起源,随后简述不同种群群体感应系统,然后介绍群体感应抑制剂定义及分类,最后回顾海洋微生物群体感应抑制剂的研究进展,从而为进一步研究群体感应抑制剂奠定基础,同时也为研发新型抗病原菌感染药物提供新的思路。     

细菌中的群体感应

群体感应(quorum sensing)是细菌根据细胞密度变化进行基因表达调控的一种生理行为。具有群体感应的细菌能产生并释放一种被称为自体诱导物(autoinducer)的信号分子,它随着细胞密度增加而同步增加。当自体诱导物积累到一定浓度时会改变细菌特定基因的表达。革兰氏阳性及阴性细菌通过群体感应与周围环境进行信息交流,从而改变细菌的一系列生理活性,这些细菌的生理特性包括共生、细菌毒性、竞争、接合、抗生素的产生、运动性、孢子及生物膜的形成。这种信号传递方式可能对低等的细胞进一步进化,并形成高等的生物体有重要作用。细菌中群体感应系统的进化可能是多细胞体形成的早期阶段。     

微生物群体感应系统的调控机制及应用研究进展

微生物通过群体感应监控范围内菌体数量并调节其自身相关基因的启动表达,进而完成对质粒的接合转移、毒力因子的表达、抗生素的产生和稳定期的进入等一系列相关生命活动的控制,因此群体感应对细菌群体的稳定有重要作用,随着对群体感应系统研究的深入,群体感应相关基因元件及调控原理逐渐清晰,也有许多群体感应系统被应用于实践中。本文中,笔者综述了几种当今研究比较清楚且有代表性的微生物群体感应系统及其调控元件,并且介绍了利用群体感应相关元件构建基因开关实现代谢流的动态调控,以及利用致病菌的群体感应实现微生物的检测及杀灭的应用。     

植物对细菌群体感应系统的反应

细菌的群体感应系统参与包括动植物病原细菌致病因子产生在内的许多生物学功能的调节。植物可以感知细菌群体感应系统及其信号分子,并作出复杂反应。植物可能受细菌群体感应信号分子诱导产生系统性防御反应,能够分泌细菌群体感应信号分子的类似物,可能产生降解细菌N-酰基高丝氨酸内酯信号分子的酶来阻断或干扰细菌群体感应系统。     

The public and private benefit of an impure public good determines the sensitivity of bacteria to population collapse in a snowdrift game

When cooperation is critical for survival, cheating can lead to population collapse. One mechanism of cooperation that permits the coexistence of cooperators and cheaters is an impure public good, whose public benefits are shared, but with a private benefit retained by the cooperator. It has yet to be determined how the contributions of the public and private benefit affect population survival. Using simulations and experiments with β-lactamase-expressing bacteria, we found that for a given amount of public and private benefit, the population was most sensitive to collapse when initiated from an intermediate fraction of cooperators due to the near-concurrent collapse of the cooperator and cheater populations. We found that increasing the ratio of public to private benefit increased sensitivity to collapse. A low ratio allowed cooperators to survive on their private benefit after the public benefit could not rescue the cheaters. A high ratio allowed the cheaters to survive to high concentrations of ampicillin due to the high public benefit. However, small increases in ampicillin caused a rapid decline in the entire population as the private benefit was insufficient to allow self-rescue of the cooperators. Our findings have implications in the persistence of populations that rely on cooperation for survival.     

Persistence of the single lineage of transmissible 'social cancer' in an asexual ant

How cooperation can arise and persist, given the threat of cheating phenotypes, is a central problem in evolutionary biology, but the actual significance of cheating in natural populations is still poorly understood. Theories of social evolution predict that cheater lineages are evolutionarily short-lived. However, an exception comes from obligate socially parasitic species, some of which thought to have arisen as cheaters within cooperator colonies and then diverged through sympatric speciation. This process requires the cheater lineage to persist by avoiding rapid extinction that would result from the fact that the cheaters inflict fitness cost on their host. We examined whether this prerequisite is fulfilled, by estimating the persistence time of cheaters in a field population of the parthenogenetic ant Pristomyrmex punctatus. Population genetic analysis found that the cheaters belong to one monophyletic lineage which we infer has persisted for 200-9200 generations. We show that the cheaters migrate and are thus horizontally transmitted between colonies, a trait allowing the lineage to avoid rapid extinction with its host colony. Although horizontal transmission of disruptive cheaters has the potential to induce extinction of the entire population, such collapse is likely averted when there is spatially restricted migration in a structured population, a scenario that matches the observed isolation by distance pattern that we found. We compare our result with other examples of disruptive and horizontally transmissible cheater lineages in nature.     

Interaction effects of cell diffusion,cell density and public goods properties on the evolution of cooperation in digital microbes

Microbial cooperation typically consists in the sharing of secreted metabolites (referred to as public goods) within the community. Although public goods generally promote population growth, they are also vulnerable to exploitation by cheating mutants, which no longer contribute, but still benefit from the public goods produced by others. Although previous studies have identified a number of key factors that prevent the spreading of cheaters, little is known about how these factors interact and jointly shape the evolution of microbial cooperation. Here, we address this issue by investigating the interaction effects of cell diffusion, cell density, public good diffusion and durability (factors known to individually influence costs and benefits of public goods production) on selection for cooperation. To be able to quantify these effects across a wide parameter space, we developed an individual‐based simulation platform, consisting of digital cooperator and cheater bacteria inhabiting a finite two‐dimensional continuous toroidal surface. Our simulations, which closely mimic microbial microcolony growth, revealed that: (i) either reduced cell diffusion (which keeps cooperators together) or reduced public good diffusion (which keeps the public goods closer to the producer) is not only essential but also sufficient for cooperation to be promoted; (ii) the sign of selection for or against cooperation can change as a function of cell density and in interaction with diffusion parameters; and (iii) increased public goods durability has opposing effects on the evolution of cooperation depending on the level of cell and public good diffusion. Our work highlights that interactions between key parameters of public goods cooperation give rise to complex fitness landscapes, a finding that calls for multifactorial approaches when studying microbial cooperation in natural systems.     

Quorum-sensing and cheating in bacterial biofilms

The idea from human societies that self-interest can lead to a breakdown of cooperation at the group level is sometimes termed the public goods dilemma. We tested this idea in the opportunistic bacterial pathogen, Pseudomonas aeruginosa, by examining the influence of putative cheats that do not cooperate via cell-to-cell signalling (quorum-sensing, QS). We found that: (i) QS cheating occurs in biofilm populations owing to exploitation of QS-regulated public goods; (ii) the thickness and density of biofilms was reduced by the presence of non-cooperative cheats; (iii) population growth was reduced by the presence of cheats, and this reduction was greater in biofilms than in planktonic populations; (iv) the susceptibility of biofilms to antibiotics was increased by the presence of cheats; and (v) coercing cooperator cells to increase their level of cooperation decreases the extent to which the presence of cheats reduces population productivity. Our results provide clear support that conflict over public goods reduces population fitness in bacterial biofilms, and that this effect is greater than in planktonic populations. Finally, we discuss the clinical implications that arise from altering the susceptibility to antibiotics.     

Microbial Communication,Cooperation and Cheating: Quorum Sensing Drives the Evolution of Cooperation in Bacteria

An increasing body of empirical evidence suggests that cooperation among clone-mates is common in bacteria. Bacterial cooperation may take the form of the excretion of “public goods”: exoproducts such as virulence factors, exoenzymes or components of the matrix in biofilms, to yield significant benefit for individuals joining in the common effort of producing them. Supposedly in order to spare unnecessary costs when the population is too sparse to supply the sufficient exoproduct level, many bacteria have evolved a simple chemical communication system called quorum sensing (QS), to “measure” the population density of clone-mates in their close neighborhood. Cooperation genes are expressed only above a threshold rate of QS signal molecule re-capture, i.e., above the local quorum of cooperators. The cooperative population is exposed to exploitation by cheaters, i.e., mutants who contribute less or nil to the effort but fully enjoy the benefits of cooperation. The communication system is also vulnerable to a different type of cheaters (“Liars”) who may produce the QS signal but not the exoproduct, thus ruining the reliability of the signal. Since there is no reason to assume that such cheaters cannot evolve and invade the populations of honestly signaling cooperators, the empirical fact of the existence of both bacterial cooperation and the associated QS communication system seems puzzling. Using a stochastic cellular automaton approach and allowing mutations in an initially non-cooperating, non-communicating strain we show that both cooperation and the associated communication system can evolve, spread and remain persistent. The QS genes help cooperative behavior to invade the population, and vice versa; cooperation and communication might have evolved synergistically in bacteria. Moreover, in good agreement with the empirical data recently available, this synergism opens up a remarkably rich repertoire of social interactions in which cheating and exploitation are commonplace.     

Kin selection-mutation balance: a model for the origin, maintenance, and consequences of social cheating

Social conflict, in the form of intraspecific selfish "cheating," has been observed in a number of natural systems. However, a formal, evolutionary genetic theory of social cheating that provides an explanatory, predictive framework for these observations is lacking. Here we derive the kin selection-mutation balance, which provides an evolutionary null hypothesis for the statics and dynamics of cheating. When social interactions have linear fitness effects and Hamilton's rule is satisfied, selection is never strong enough to eliminate recurrent cheater mutants from a population, but cheater lineages are transient and do not invade. Instead, cheating lineages are eliminated by kin selection but are constantly reintroduced by mutation, maintaining a stable equilibrium frequency of cheaters. The presence of cheaters at equilibrium creates a "cheater load" that selects for mechanisms of cheater control, such as policing. We find that increasing relatedness reduces the cheater load more efficiently than does policing the costs and benefits of cooperation. Our results provide new insight into the effects of genetic systems, mating systems, ecology, and patterns of sex-limited expression on social evolution. We offer an explanation for the widespread cheater/altruist polymorphism found in nature and suggest that the common fear of conflict-induced social collapse is unwarranted.     

Looking for loss in all the wrong places: loss avoidance does not explain cheater detection

The ability to detect cheaters has been proposed as an adaptive design feature of psychological adaptations for cooperation. This proposal has been tested with studies on the Wason selection task, which purportedly demonstrate that humans possess a specific competence for detecting cheaters in cooperative interactions. An alternative set of theories suggests that people are not looking for cheaters per se, but are looking for losses in an effort to maximize their utility. In previous investigations of cheater detection, cheating has been confounded with someone suffering a loss. We sought to test rival accounts of cheater detection by devising versions of the selection task in which cheating is unconfounded with losses. The results suggest that people are competent at detecting cheaters even when no losses are involved, lending support to the view that cheater detection is a specific design feature of psychological adaptations for cooperation.     

A common evolutionary pathway for maintaining quorum sensing in <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>

In the bacterium Pseudomonas aeruginosa, the synthesis and secretion of extracellular protease is a typical cooperative behavior regulated by quorum sensing. However, this type of cooperative behavior is easily exploited by other individuals who do not synthesize public goods, which is known as the “tragedy of the commons”. Here P. aeruginosa was inoculated into casein media with different nitrogen salts added. In casein broth, protease (a type of public good) is necessary for bacterial growth. After 30 days of sequential transfer, some groups propagated stably and avoided “tragedy of the commons”. The evolved cooperators who continued to synthesize protease were isolated from these stable groups. By comparing the characteristics of quorum sensing in these cooperators, an identical evolutionary pattern was found. A variety of cooperative behaviors regulated by quorum sensing, such as the synthesis and secretion of protease and signals, were significantly reduced during the process of evolution. Such reductions improved the efficiency of cooperation, helping to prevent cheating. In addition, the production of pyocyanin, which is regulated by the RhlIR system, increased during the process of evolution, possibly due to its role in stabilizing the cooperation. This study contributes towards our understanding of the evolution of quorum sensing of P. aeruginosa.