Quorum sensing inhibitors: An overview

Excessive and indiscriminate use of antibiotics to treat bacterial infections has lead to the emergence of multiple drug resistant strains. Most infectious diseases are caused by bacteria which proliferate within quorum sensing (QS) mediated biofilms. Efforts to disrupt biofilms have enabled the identification of bioactive molecules produced by prokaryotes and eukaryotes. These molecules act primarily by quenching the QS system. The phenomenon is also termed as quorum quenching (QQ). In addition, synthetic compounds have also been found to be effective in QQ. This review focuses primarily on natural and synthetic quorum sensing inhibitors (QSIs) with the potential for treating bacterial infections. It has been opined that the most versatile prokaryotes to produce QSI are likely to be those, which are generally regarded as safe. Among the eukaryotes, certain legumes and traditional medicinal plants are likely to act as QSIs. Such findings are likely to lead to efficient treatments with much lower doses of drugs especially antibiotics than required at present.     

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.     

Quorum sensing in Serratia

Many bacteria use cell-cell communication to monitor their population density, synchronize their behaviour and socially interact. This communication results in a coordinated gene regulation and is generally called quorum sensing. In gram-negative bacteria, the most common quorum signal molecules are acylated homoserine lactones (AHLs), although other low-molecular-mass signalling molecules have been described such as Autoinducer-2 (AI-2). The phenotypes that are regulated in Serratia species by means of AHLs are remarkably diverse and of profound biological and ecological significance, and often interconnected with other global regulators. Furthermore, AHL- and AI-2-mediated systems (less profoundly studied) are continuously being discovered and explored in Serratia spp., many having interesting twists on the basic theme. Therefore, this review will highlight the current known quorum sensing systems in Serratia spp., including the important nosocomial pathogen Serratia marcescens.     

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 and communication in bacteria

Bacteria are able “to sense” an increase in the cell population density and to respond to it by the induction of special sets of genes. This type of regulation, called Quorum Sensing (QS), includes the production and excretion of low-molecular-weight signaling molecules (autoinducers, AI), which diffuse readily through the cell wall, from cells into the medium. As the bacterial population reaches the critical level of density, the concentration of these signaling molecules in the medium increases as a function of population density. On reaching the critical threshold concentration, AIs bind to specific receptor regulatory proteins, which induce the expression of target genes. By means of AIs, bacteria accomplish the communication that is the transmission of information between bacteria belonging to the same or different species, genera, and even families: the signaling molecules of some bacteria affect the receptors of others causing a coordinated reply of cells of the bacterial population. Bacteria of different taxonomic groups use the QS systems in regulation of a broad range of physiological activities. These processes include virulence, symbiosis, conjugation, biofilm formation, bioluminescence, synthesis of enzymes, antibiotic substances, etc. Here we review different QS systems of bacteria, the role of QS in bacterial communication, and some applied aspects of QS regulation application.     

Quorum sensing: the many languages of bacteria

In the conventional view of prokaryotic existence, bacteria live unicellularly, with responses to external stimuli limited to the detection of chemical and physical signals of environmental origin. This view of bacteriology is now recognized to be overly simplistic, because bacteria communicate with each other through small 'hormone-like' organic compounds referred to as autoinducers. These bacterial cell-to-cell signaling systems were initially described as mechanisms through which bacteria regulate gene expression via cell density and, therefore, they have been collectively termed quorum sensing. The functions controlled by quorum sensing are varied and reflect the needs of a particular species of bacteria to inhabit a given niche. Three major quorum-sensing circuits have been described: one used primarily by Gram-negative bacteria, one used primarily by Gram-positive bacteria, and one that has been proposed to be universal.     

Quorum sensing inhibitors as antipathogens: biotechnological applications

The mechanisms through which microbes communicate using signal molecules has inspired a great deal of research. Microbes use this exchange of information, known as quorum sensing (QS), to initiate and perpetuate infectious diseases in eukaryotic organisms, evading the eukaryotic defense system by multiplying and expressing their pathogenicity through QS regulation. The major issue to arise from such networks is increased bacterial resistance to antibiotics, resulting from QS-dependent mediation of the formation of biofilm, the induction of efflux pumps, and the production of antibiotics. QS inhibitors (QSIs) of diverse origins have been shown to act as potential antipathogens. In this review, we focus on the use of QSIs to counter diseases in humans as well as plants and animals of economic importance. We also discuss the challenges encountered in the potential applications of QSIs.     

Quorum sensing: alcohols in a social situation

Many microbes use extracellular signals to transmit information about population density and environmental conditions. Recent evidence suggests that the budding yeast Saccharomyces cerevisiae exhibits this type of regulation and that the signals are aromatic alcohols.     

Quorum sensing and the lifestyle of Yersinia

Bacterial cell-to-cell communication ('quorum sensing') is mediated by structurally diverse, small diffusible signal molecules which regulate gene expression as a function of cell population density. Many different Gram-negative animal, plant and fish pathogens employ N-acylhomoserine lactones (AHLs) as quorum sensing signal molecules which control diverse physiological processes including bioluminescence, swarming, antibiotic biosynthesis, plasmid conjugal transfer, biofilm development and virulence. AHL-dependent quorum sensing is highly conserved in both pathogenic and non-pathogenic members of the genus Yersinia. Yersinia pseudotuberculosis for example, produces at least eight different AHLs and possesses two homologues of the LuxI family of AHL synthases and two members of the LuxR family of AHL-dependent response regulators. In all Yersinia species so far examined, the genes coding for LuxR and LuxI homologues are characteristically arranged convergently and overlapping. In Y. pseudotuberculosis AHL-dependent quorum sensing is involved in the control of cell aggregation and swimming motility, the latter via the flagellar regulatory cascade. This is also the case for swimming and also swarming motility in Yersinia enterocolitica. Howeverthe role of AHL-dependent quorum sensing in Yersinia pestis remains to be determined.     

Quorum sensing and silencing in Vibrio parahaemolyticus

The quorum regulatory cascade is poorly characterized in Vibrio parahaemolyticus, in part because swarming and virulence factors--the hallmarks of the organism--are repressed by this scheme of gene control, and quorum sensing seems to be silenced in many isolates. In these studies, we examine a swarming-proficient, virulent strain and identify an altered-function allele of the quorum regulator luxO that is demonstrated to produce a constitutively active mimic of LuxO～P. We find that LuxO* affects the expression of three small regulatory RNAs (Qrrs) and the activity of a translational fusion in opaR, the output regulator. Tests for epistasis showed that luxO* is dominant over luxO and that opaR is dominant over luxO. Thus, information flow through the central elements of the V. parahaemolyticus quorum pathway is proven for the first time. Quorum-sensing output was explored using microarray profiling: the OpaR regulon encompasses ～5.2% of the genome. OpaR represses the surface-sensing and type III secretion system 1 (T3SS1) regulons. One novel discovery is that OpaR strongly and oppositely regulates two type VI secretion systems (T6SS). New functional consequences of OpaR control were demonstrated: OpaR increases the cellular cyclic di-GMP (c-di-GMP) level, positively controls chitin-induced DNA competency, and profoundly blocks cytotoxicity toward host cells. In expanding the previously known quorum effects beyond the induction of the capsule and the repression of swarming to elucidate the global scope of genes in the OpaR regulon, this study yields many clues to distinguishing traits of this Vibrio species; it underscores the profoundly divergent survival strategies of the quorum On/Off phase variants.