The development of novel therapies to control diseases caused by antibiotic-resistant pathogens is one of the major challenges we are currently facing. Many important plant, animal, and human ...pathogens regulate virulence by quorum sensing, bacterial cell-to-cell communication with small signal molecules. Consequently, a significant research effort is being undertaken to identify and use quorum-sensing-interfering agents in order to control diseases caused by these pathogens. In this review, an overview of our current knowledge of quorum-sensing systems of Gram-negative model pathogens is presented as well as the link with virulence of these pathogens, and recent advances and challenges in the development of quorum-sensing-interfering therapies are discussed.
Research over the past decades has shown that bacteria communicate with each other with small signal molecules in a process that has been termed quorum sensing, and the list of bacterial quorum-sensing molecules is still growing.
The virulence of many bacterial pathogens of plants, animals, and humans is controlled by quorum sensing, and quorum-sensing-interference is one of the most intensively studied strategies for controlling disease caused by antibiotic-resistant bacteria.
Various quorum-sensing-interfering agents have been described in recent years, including natural and synthetic compounds, enzymes, and antibodies, and these agents have been proven to attenuate bacterial disease in animal and plant models.
The theory of persisting independent and isolated regarding microorganisms is no longer accepted. To survive and reproduce they have developed several communication platforms within the cells which ...facilitates them to adapt the surrounding environmental changes. This cell-to-cell communication is termed as quorum sensing; it relies upon the cell density and can stimulate several traits of microbes including biofilm formation, competence, and virulence factors secretion. Initially, this sophisticated mode of communication was discovered in bacteria; later, it was also confirmed in eukaryotes (fungi). As a consequence, many quorum-sensing molecules and inhibitors have been identified and characterized in various fungal species. In this review article, we will primarily focus on fungal quorum-sensing molecules and the production of inhibitors from fungal species with potential applications for combating fungal infections.
This Review highlights how we can build upon the relatively new and rapidly developing field of research into bacterial quorum sensing (QS). We now have a depth of knowledge about how bacteria use QS ...signals to communicate with each other and to coordinate their activities. In recent years there have been extraordinary advances in our understanding of the genetics, genomics, biochemistry, and signal diversity of QS. We are beginning to understand the connections between QS and bacterial sociality. This foundation places us at the beginning of a new era in which researchers will be able to work towards new medicines to treat devastating infectious diseases, and use bacteria to understand the biology of sociality.
Vibrio cholerae uses a quorum-sensing (QS) system composed of the autoinducer 3,5-dimethylpyrazin-2-ol (DPO) and receptor VqmA (VqmAVc), which together repress genes for virulence and biofilm ...formation. vqmA genes exist in Vibrio and in one vibriophage, VP882. Phage-encoded VqmA (VqmAPhage) binds to host-produced DPO, launching the phage lysis program via an antirepressor that inactivates the phage repressor by sequestration. The antirepressor interferes with repressors from related phages. Like phage VP882, these phages encode DNA-binding proteins and partner antirepressors, suggesting that they, too, integrate host-derived information into their lysis-lysogeny decisions. VqmAPhage activates the host VqmAVc regulon, whereas VqmAVc cannot induce phage-mediated lysis, suggesting an asymmetry whereby the phage influences host QS while enacting its own lytic-lysogeny program without interference. We reprogram phages to activate lysis in response to user-defined cues. Our work shows that a phage, causing bacterial infections, and V. cholerae, causing human infections, rely on the same signal molecule for pathogenesis.
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•A phage encodes a quorum-sensing receptor that detects a host-produced autoinducer•Phage detection of the autoinducer controls the phage lytic-lysogeny fate switch•A new phage protein, Qtip, sequesters and inactivates the phage cI repressor•Recombinant phages are engineered to execute lysis in response to user-defined cues
Bacteriophages can “listen in” on their host bacterium’s quorum-sensing systems, shifting their lysis-lysogeny decisions based on host cell density.
Bacteria commonly exist in high cell density populations, making them prone to viral predation and horizontal gene transfer (HGT) through transformation and conjugation. To combat these invaders, ...bacteria possess an arsenal of defenses, such as CRISPR-Cas adaptive immunity. Many bacterial populations coordinate their behavior as cell density increases, using quorum sensing (QS) signaling. In this study, we demonstrate that QS regulation results in increased expression of the type I-E, I-F, and III-A CRISPR-Cas systems in Serratia cells in high-density populations. Strains unable to communicate via QS were less effective at defending against invaders targeted by any of the three CRISPR-Cas systems. Additionally, the acquisition of immunity by the type I-E and I-F systems was impaired in the absence of QS signaling. We propose that bacteria can use chemical communication to modulate the balance between community-level defense requirements in high cell density populations and host fitness costs of basal CRISPR-Cas activity.
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•Quorum sensing regulates the type I-E, I-F, and III-A CRISPR-Cas systems in Serratia•SmaR represses cas gene and CRISPR expression in the absence of AHL signals•Both interference and adaptation are modulated by quorum sensing•Bacteria coordinate their defenses based on cell density and the risk of infection
Patterson et al. examined quorum sensing and the function of three CRISPR-Cas systems in Serratia. They discovered that bacteria can use chemical communication to coordinate CRISPR-Cas immune defenses at high cell densities.
Quorum sensing (QS), a density-dependent signaling mechanism of microbial cells, involves an exchange and sense of low molecular weight signaling compounds called autoinducers. With the increase in ...population density, the autoinducers accumulate in the extracellular environment and once their concentration reaches a threshold, many genes are either expressed or repressed. This cell density-dependent signaling mechanism enables single cells to behave as multicellular organisms and regulates different microbial behaviors like morphogenesis, pathogenesis, competence, biofilm formation, bioluminescence, etc guided by environmental cues. Initially, QS was regarded to be a specialized system of certain bacteria. The discovery of filamentation control in pathogenic polymorphic fungus Candida albicans by farnesol revealed the phenomenon of QS in fungi as well. Pathogenic microorganisms primarily regulate the expression of virulence genes using QS systems. The indirect role of QS in the emergence of multiple drug resistance (MDR) in microbial pathogens necessitates the finding of alternative antimicrobial therapies that target QS and inhibit the same. A related phenomenon of quorum sensing inhibition (QSI) performed by small inhibitor molecules called quorum sensing inhibitors (QSIs) has an ability for efficient reduction of gene expression regulated by quorum sensing. In the present review, recent advancements in the study of different fungal quorum sensing molecules (QSMs) and quorum sensing inhibitors (QSIs) of fungal origin along with their mechanism of action and/or role/s are discussed.
•Bacterial adhesion biomass was significantly improved by exogenous AHLs.•Appropriate AHLs that promote bacterial adhesion were selected.•The preferred form of AHL and QS response differed for ...various biofilms.•A potential way to improve the settling property of bulking sludge was proposed.
Quorum sensing (QS) plays a crucial role during initial biofilm formation, however the QS threshold and the response of biofilm formation towards N-acyl-homoserine lactones (AHLs) remains largely unknown due to the limitation of nondestructive online methods for monitoring bacterial adherence and the complexity of QS system, which limits the application of QS signal reagents in biofilm reactors. In this study, bacterial QS threshold and its response of biofilm formation to AHLs in purely cultured Sphingomonas rubra biofilm as well as in three different wastewater biofilms #1–3 were investigated via real time cell analysis (RTCA). The main perspective was to study the biomass adherence in response to 12 different forms of AHLs at different concentrations. Results showed that bacterial adhesion was significantly improved by exogenous AHLs with the maximum increase of 2.26-, 2.36-, 2.52-, and 2.80- times biomass production in the four respective biofilms. Although the preferred form of AHL differed for various biofilms, the long-chain AHLs (12–14 carbons) resulted in an overall improvement of bacterial adhesion due to their stronger hydrophobicity and hydrolysis resistance. In addition, bacterial QS threshold of AHLs was observed to have a wide range of concentration from 10 ng/L to 10 μg/L. Meanwhile, QS response time to AHLs also showed a significant difference in different biofilms. Biofilm #2 inoculated with bulking sludge had lower QS threshold of 10 ng/L and faster response to most AHLs that is less than 6 h. Thus, considering the improvement of biofilm adhesion by AHLs, 10 ng/L of C12-HSL, 10 ng/L of C12-HSL, and 10 ng/L of C6-HSL were preferentially selected for wastewater biofilms #1–3 respectively. Unexpectedly, adding high-concentration of AHLs detected in sludges did not significantly improved the bacterial adhesion. Infact the addition of these AHLs at low concentrations or even undetected concentrations substantially improved bacterial adhesion, which could be explained by bacterial communities composition. According to the Pearson correlation analysis, 62% of the top 50 most abundant genera in bacterial communities were significantly negatively related to the response time of multiple AHLs, representing their fast QS response. The QS bacteria, Dechloromonas and Nitrospira have fast QS response for C4-HSL and C8-HSL while, Comamonadaceae has fast QS response for 3OC8-HSL, 3OC10-HSL, 3OC12-HSL, and 3OC14-HSL. In contrast, the rest 38% of the top most abundant genera, such as Ferruginibacter, Hyphomicrobium, and Terrimonas quickly responded to only one AHL, showing significant negative relationship with the response time of C6-HSL. Overall, this study provides an effective and convenient means to select appropriate AHL reagents to promote bacterial adhesion in biofilm systems. Moreover, it also suggests that exogenous AHLs may be useful in improving the settling property of bulking sludge.
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Quorum sensing (QS) refers to the capacity of bacteria to monitor their population density and regulate gene expression accordingly: the QS-regulated processes deal with multicellular behaviors (e.g. ...growth and development of biofilm), horizontal gene transfer and host–microbe (symbiosis and pathogenesis) and microbe–microbe interactions. QS signaling requires the synthesis, exchange and perception of bacterial compounds, called autoinducers or QS signals (e.g. N-acylhomoserine lactones). The disruption of QS signaling, also termed quorum quenching (QQ), encompasses very diverse phenomena and mechanisms which are presented and discussed in this review. First, we surveyed the QS-signal diversity and QS-associated responses for a better understanding of the targets of the QQ phenomena that organisms have naturally evolved and are currently actively investigated in applied perspectives. Next the mechanisms, targets and molecular actors associated with QS interference are presented, with a special emphasis on the description of natural QQ enzymes and chemicals acting as QS inhibitors. Selected QQ paradigms are detailed to exemplify the mechanisms and biological roles of QS inhibition in microbe–microbe and host–microbe interactions. Finally, some QQ strategies are presented as promising tools in different fields such as medicine, aquaculture, crop production and anti-biofouling area.
Bacterial quorum sensing-mediated signalling can be disrupted by a wide variety of phenomena collectively known as quorum quenching: the mechanisms behind this inhibition, their biological and ecological impact in microbe-microbe and host-microbe interactions, as well as some of the most recent developments of their applications in human health, agriculture, aquaculture and environmentally-friendly technologies, are presented and discussed in this review.
Graphical Abstract Figure.
Bacterial quorum sensing-mediated signalling can be disrupted by a wide variety of phenomena collectively known as quorum quenching: the mechanisms behind this inhibition, their biological and ecological impact in microbe-microbe and host-microbe interactions, as well as some of the most recent developments of their applications in human health, agriculture, aquaculture and environmentally-friendly technologies, are presented and discussed in this review.
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