Emerging trends in the inhibition of bacterial molecular communication: An overview.

Quorum sensing (QS) is a molecular cell-cell communication utilized by several bacteria and some fungi. It involves cell density dependent gene expression that includes extra polymeric substance production, sporulation, antibiotic production, motility, competence, symbiosis and conjugation. These expressions were carried out by different signaling molecules like acyl homo-serine lactone (AHL) and auto-inducing peptides (AIPs) which was effluxed by gram negative and gram positive bacteria. Pathogenic bacteria and biofilms often exhibit high resistance to antibiotics, attributed to the presence of antibiotic efflux pumps, reduced membrane permeability, and enzymes that deactivate quorum sensing (QS) inhibitors. To counteract virulence and multi-drug resistance (MDR), novel strategies such as employing quorum sensing (QS) inhibitors and quorum quenchers are employed. It targets signaling molecules with synthesis and prevents the signal from binding to receptors. In this present review, the mechanisms of QS along with inhibitors from different sources are described. These strategies potentially interfere with QS and it can be applied in different fields, mainly in hospitals and marine environments where the pathogenic infections and biofilm formation are highly involved.

Deciphering the dynamics of methicillin-resistant Staphylococcus aureus biofilm formation: from molecular signaling to nanotherapeutic advances.

Methicillin-resistant Staphylococcus aureus (MRSA) represents a global threat, necessitating the development of effective solutions to combat this emerging superbug. In response to selective pressures within healthcare, community, and livestock settings, MRSA has evolved increased biofilm formation as a multifaceted virulence and defensive mechanism, enabling the bacterium to thrive in harsh conditions. This review discusses the molecular mechanisms contributing to biofilm formation across its developmental stages, hence representing a step forward in developing promising strategies for impeding or eradicating biofilms. During staphylococcal biofilm development, cell wall-anchored proteins attach bacterial cells to biotic or abiotic surfaces; extracellular polymeric substances build scaffolds for biofilm formation; the cidABC operon controls cell lysis within the biofilm, and proteases facilitate dispersal. Beside the three main sequential stages of biofilm formation (attachment, maturation, and dispersal), this review unveils two unique developmental stages in the biofilm formation process for MRSA; multiplication and exodus. We also highlighted the quorum sensing as a cell-to-cell communication process, allowing distant bacterial cells to adapt to the conditions surrounding the bacterial biofilm. In S. aureus, the quorum sensing process is mediated by autoinducing peptides (AIPs) as signaling molecules, with the accessory gene regulator system playing a pivotal role in orchestrating the production of AIPs and various virulence factors. Several quorum inhibitors showed promising anti-virulence and antibiofilm effects that vary in type and function according to the targeted molecule. Disrupting the biofilm architecture and eradicating sessile bacterial cells are crucial steps to prevent colonization on other surfaces or organs. In this context, nanoparticles emerge as efficient carriers for delivering antimicrobial and antibiofilm agents throughout the biofilm architecture. Although metal-based nanoparticles have been previously used in combatting biofilms, its non-degradability and toxicity within the human body presents a real challenge. Therefore, organic nanoparticles in conjunction with quorum inhibitors have been proposed as a promising strategy against biofilms. As nanotherapeutics continue to gain recognition as an antibiofilm strategy, the development of more antibiofilm nanotherapeutics could offer a promising solution to combat biofilm-mediated resistance.

Molecular Aspects of the Functioning of Pathogenic Bacteria Biofilm Based on Quorum Sensing (QS) Signal-Response System and Innovative Non-Antibiotic Strategies for Their Elimination.

One of the key mechanisms enabling bacterial cells to create biofilms and regulate crucial life functions in a global and highly synchronized way is a bacterial communication system called quorum sensing (QS). QS is a bacterial cell-to-cell communication process that depends on the bacterial population density and is mediated by small signalling molecules called autoinducers (AIs). In bacteria, QS controls the biofilm formation through the global regulation of gene expression involved in the extracellular polymeric matrix (EPS) synthesis, virulence factor production, stress tolerance and metabolic adaptation. Forming biofilm is one of the crucial mechanisms of bacterial antimicrobial resistance (AMR). A common feature of human pathogens is the ability to form biofilm, which poses a serious medical issue due to their high susceptibility to traditional antibiotics. Because QS is associated with virulence and biofilm formation, there is a belief that inhibition of QS activity called quorum quenching (QQ) may provide alternative therapeutic methods for treating microbial infections. This review summarises recent progress in biofilm research, focusing on the mechanisms by which biofilms, especially those formed by pathogenic bacteria, become resistant to antibiotic treatment. Subsequently, a potential alternative approach to QS inhibition highlighting innovative non-antibiotic strategies to control AMR and biofilm formation of pathogenic bacteria has been discussed.

It is the time for quorum sensing inhibition as alternative strategy of antimicrobial therapy.

Multiple drug resistance poses a significant threat to public health worldwide, with a substantial increase in morbidity and mortality rates. Consequently, searching for novel strategies to control microbial pathogenicity is necessary. With the aid of auto-inducers (AIs), quorum sensing (QS) regulates bacterial virulence factors through cell-to-cell signaling networks. AIs are small signaling molecules produced during the stationary phase. When bacterial cultures reach a certain level of growth, these molecules regulate the expression of the bound genes by acting as mirrors that reflect the inoculum density.Gram-positive bacteria use the peptide derivatives of these signaling molecules, whereas Gram-negative bacteria use the fatty acid derivatives, and the majority of bacteria can use both types to modulate the expression of the target gene. Numerous natural and synthetic QS inhibitors (QSIs) have been developed to reduce microbial pathogenesis. Applications of QSI are vital to human health, as well as fisheries and aquaculture, agriculture, and water treatment. Video Abstract.

Conversations in the Gut: The Role of Quorum Sensing in Normobiosis.

An imbalance in gut microbiota, termed dysbiosis, has been shown to affect host health. Several factors, including dietary changes, have been reported to cause dysbiosis with its associated pathologies that include inflammatory bowel disease, cancer, obesity, depression, and autism. We recently demonstrated the inhibitory effects of artificial sweeteners on bacterial quorum sensing (QS) and proposed that QS inhibition may be one mechanism behind such dysbiosis. QS is a complex network of cell-cell communication that is mediated by small diffusible molecules known as autoinducers (AIs). Using AIs, bacteria interact with one another and coordinate their gene expression based on their population density for the benefit of the whole community or one group over another. Bacteria that cannot synthesize their own AIs secretly "listen" to the signals produced by other bacteria, a phenomenon known as "eavesdropping". AIs impact gut microbiota equilibrium by mediating intra- and interspecies interactions as well as interkingdom communication. In this review, we discuss the role of QS in normobiosis (the normal balance of bacteria in the gut) and how interference in QS causes gut microbial imbalance. First, we present a review of QS discovery and then highlight the various QS signaling molecules used by bacteria in the gut. We also explore strategies that promote gut bacterial activity via QS activation and provide prospects for the future.

The Role of Intercellular Signaling in the Regulation of Bacterial Adaptive Proliferation.

Bacterial adaptation is regulated at the population level with the involvement of intercellular communication (quorum sensing). When the population density is insufficient for adaptation under starvation, bacteria can adjust it to a quorum level through cell divisions at the expense of endogenous resources. This phenomenon has been described for the phytopathogenic bacterium Pectobacterium atrosepticum (Pba), and it is called, in our study, adaptive proliferation. An important attribute of adaptive proliferation is its timely termination, which is necessary to prevent the waste of endogenous resources when the required level of population density is achieved. However, metabolites that provide the termination of adaptive proliferation remained unidentified. We tested the hypothesis of whether quorum sensing-related autoinducers prime the termination of adaptive proliferation and assessed whether adaptive proliferation is a common phenomenon in the bacterial world. We showed that both known Pba quorum sensing-related autoinducers act synergistically and mutually compensatory to provide the timely termination of adaptive proliferation and formation of cross-protection. We also demonstrated that adaptive proliferation is implemented by bacteria of many genera and that bacteria with similar quorum sensing-related autoinducers have similar signaling backgrounds that prime the termination of adaptive proliferation, enabling the collaborative regulation of this adaptive program in multispecies communities.

Escherichia coli minicells with targeted enzymes as bioreactors for producing toxic compounds.

Formed by aberrant cell division, minicells possess functional metabolism despite their inability to grow and divide. Minicells exhibit not only superior stability when compared with bacterial cells but also exceptional tolerance-characteristics that are essential for a de novo bioreactor platform. Accordingly, we engineered minicells to accumulate protein, ensuring sufficient production capability. When tested with chemicals regarded as toxic against cells, the engineered minicells produced titers of C6-C10 alcohols and esters, far surpassing the corresponding production from bacterial cells. Additionally, microbial autoinducer production that is limited in expanding bacterial population was conducted in the minicells. Because bacterial population growth was nonexistent, the minicells produced autoinducers in constant amounts, which allowed precise control of the bacterial population having autoinducer-responsive gene circuits. When bacterial population growth was nonexistent, the minicells produced autoinducers in constant amounts, which allowed precise control of the bacterial population having autoinducer-based gene circuits with the minicells. This study demonstrates the potential of minicells as bioreactors suitable for products with known limitations in microbial production, thus providing new possibilities for bioreactor engineering.

Quorum sensing mediates gut bacterial communication and host-microbiota interaction.

Gut bacteria employ quorum sensing (QS) to coordinate their activities and communicate with one another, this process relies on the production, detection, and response to autoinducers, which are extracellular signaling molecules. In addition to synchronizing behavioral activities within the species, QS plays a crucial role in the gut host-microbiota interaction. In this review, an overview of classical QS systems is presented as well as the interspecies communication mediated by QS, and recent advances in the host-microbiota interaction mediated by QS. A greater knowledge of the communication network of gut microbiota is not only an opportunity and a challenge for developing nutritional and therapeutic strategies against bacterial illnesses, but also a means for improving gut health.

Exploring the Function of Quorum Sensing Regulated Biofilms in Biological Wastewater Treatment: A Review.

Quorum sensing (QS), a type of bacterial cell-cell communication, produces autoinducers which help in biofilm formation in response to cell population density. In this review, biofilm formation, the role of QS in biofilm formation and development with reference to biological wastewater treatment are discussed. Autoinducers, for example, acyl-homoserine lactones (AHLs), auto-inducing oligo-peptides (AIPs) and autoinducer 2, present in both Gram-negative and Gram-positive bacteria, with their mechanism, are also explained. Over the years, wastewater treatment (WWT) by QS-regulated biofilms and their optimization for WWT have gained much attention. This article gives a comprehensive review of QS regulation methods, QS enrichment methods and QS inhibition methods in biological waste treatment systems. Typical QS enrichment methods comprise adding QS molecules, adding QS accelerants and cultivating QS bacteria, while typical QS inhibition methods consist of additions of quorum quenching (QQ) bacteria, QS-degrading enzymes, QS-degrading oxidants, and QS inhibitors. Potential applications of QS regulated biofilms for WWT have also been summarized. At last, the knowledge gaps present in current researches are analyzed, and future study requirements are proposed.

Microbe Related Chemical Signalling and Its Application in Agriculture.

The agriculture sector has been put under tremendous strain by the world's growing population. The use of fertilizers and pesticides in conventional farming has had a negative impact on the environment and human health. Sustainable agriculture attempts to maintain productivity, while protecting the environment and feeding the global population. The importance of soil-dwelling microbial populations in overcoming these issues cannot be overstated. Various processes such as rhizospheric competence, antibiosis, release of enzymes, and induction of systemic resistance in host plants are all used by microbes to influence plant-microbe interactions. These processes are largely founded on chemical signalling. Producing, releasing, detecting, and responding to chemicals are all part of chemical signalling. Different microbes released distinct sorts of chemical signal molecules which interacts with the environment and hosts. Microbial chemicals affect symbiosis, virulence, competence, conjugation, antibiotic production, motility, sporulation, and biofilm growth, to name a few. We present an in-depth overview of chemical signalling between bacteria-bacteria, bacteria-fungi, and plant-microbe and the diverse roles played by these compounds in plant microbe interactions. These compounds' current and potential uses and significance in agriculture have been highlighted.

Regulatory and innovative mechanisms of bacterial quorum sensing-mediated pathogenicity: a review.

Quorum sensing (QS) is a system of bacteria in which cells communicate with each other; it is linked to cell density in the microbiome. The high-density colony population can provide enough small molecular signals to enable a range of cellular activities, gene expression, pathogenicity, and antibiotic resistance that cause damage to the hosts. QS is the basis of chronic illnesses in human due to microbial sporulation, expression of virulence factors, biofilm formation, secretion of enzymes, or production of membrane vesicles. The transfer of antimicrobial resistance gene (ARG) among antibiotic resistance bacteria is a major public health concern. QS-mediated biofilm is a hub for ARG horizontal gene transfer. To develop innovative approach to prevent microbial pathogenesis, it is essential to understand the role of QS especially in response to environmental stressors such as exposure to antibiotics. This review provides the latest knowledge on the relationship of QS and pathogenicity and explore the novel approach to control QS via quorum quenching (QQ) using QS inhibitors (QSIs) and QQ enzymes. The state-of-the art knowledge on the role of QS and the potential of using QQ will help to overcome the threats of rapidly emerging bacterial pathogenesis.

Quorum sensing system: Target to control the spread of bacterial infections.

Quorum Sensing (QS) systems regulate the gene expression of different types of virulence factors in accordance with the cell population density. A literature search was performed, including electronic databases such as MEDLINE/PubMed, SciELO, and LILACS, as well as other databases not indexed, such as Google Scholar. The search was conducted between July 2018 and April 2019, through online research. Antimicrobial resistance is one of the biggest threats to global health and the dissemination of resistant microbes in the environment is a major public health problem. Therefore, it is important to develop new therapies to control the spread of resistant bacteria to humans. Thus, interference in the chemical signal (autoinducers) of the QS system has been postulated as a good alternative, technically known as "Quorum Quenching" or QS inhibitors. Inhibition of QS signaling is not intended to kill the microorganism, but to block the expression of the target genes, making the cells less virulent and more vulnerable to host immune response. Anti-virulence therapy by agents that interfere with this system in pathogenic bacteria is a well-studied strategy, including medicinal plants and their bioactive constituents, and presents good prospects. This review aims to provide an overview of the QS system in bacteria and describe the main inhibitors of the system.

Quorum sensing in Vibrio spp.: the complexity of multiple signalling molecules in marine and aquatic environments.

Quorum sensing (QS) is a density-dependent mechanism enabling bacteria to coordinate their actions via the release of small diffusible molecules named autoinducers (AIs). Vibrio spp. are able to adapt to changing environmental conditions by using a wide range of physiological mechanisms and many species pose a threat for human health and diverse marine and estuarine ecosystems worldwide. Cell-to-cell communication controls many of their vital functions such as niche colonization, survival strategies, or virulence. In this review, I summarize (1) the different known QS pathways (2) the diversity of AIs as well as their biological functions, and (3) the QS-mediated interactions between Vibrio and other organisms. However, the current knowledge is limited to a few pathogenic or bioluminescent species and in order to provide a genus-wide view an inventory of QS genes among 87 Vibrio species has been made. The large diversity of signal molecules and their differential effects on a particular physiological function suggest that the complexity of multiple signalling systems within bacterial communities is far from being fully understood. I question here the real level of specificity of such communication in the environment and discuss the different perspectives in order to better apprehend QS in natural habitats.

Developments in strategies for Quorum Sensing virulence factor inhibition to combat bacterial drug resistance.

Quorum sensing (QS) is a complex bacterial intercellular communication system. It is mediated by molecules called auto-inducers (AIs) and allows coordinated responses to a variety of environmental signals by inducing alterations in gene expression. Communication through QS can tremendously stimulate the pathogenicity and virulence via multiple mechanisms in pathogenic bacteria. The present review explores the major types of multitudinous QS systems known in Gram-positive and Gram-negative bacteria and their roles in bacterial pathogenesis and drug resistance. Because bacterial resistance to antibiotics is increasingly becoming a significant clinical challenge to human health; alternate strategies to combat drug resistance are warranted. Targeting bacterial pathogenicity by interruptions in QS using natural QS inhibitors and synthetic quorum-quenching analogs are being increasingly considered for development of next generation antimicrobials. The review highlights the recent advancements in discovery of promising new QS modulators and their efficiency in controlling infections caused by multidrug-resistant bacterial pathogens.

An Unprecedented Medium-Chain Diunsaturated N-acylhomoserine Lactone from Marine Roseobacter Group Bacteria.

N-acylhomoserine lactones (AHLs), bacterial signaling compounds involved in quorum-sensing, are a structurally diverse group of compounds. We describe here the identification, synthesis, occurrence and biological activity of a new AHL, N-((2E,5Z)-2,5-dodecadienoyl)homoserine lactone (11) and its isomer N-((3E,5Z)-3,5-dodecadienoyl)homoserine lactone (13), occurring in several Roseobacter group bacteria (Rhodobacteraceae). The analysis of 26 strains revealed the presence of 11 and 13 in six of them originating from the surface of the macroalgae Fucus spiralis or sediments from the North Sea. In addition, 18 other AHLs were detected in 12 strains. Compound identification was performed by GC/MS. Mass spectral analysis revealed a diunsaturated C12 homoserine lactone as structural element of the new AHL. Synthesis of three likely candidate compounds, 11, 13 and N-((2E,4E)-2,4-dodecadienoyl)homoserine lactone (5), revealed the former to be the natural AHLs. Bioactivity test with quorum-sensing reporter strains showed high activity of all three compounds. Therefore, the configuration and stereochemistry of the double bonds in the acyl chain seemed to be unimportant for the activity, although the chains have largely different shapes, solely the chain length determining activity. In combination with previous results with other Roseobacter group bacteria, we could show that there is wide variance between AHL composition within the strains. Furthermore, no association of certain AHLs with different habitats like macroalgal surfaces or sediment could be detected.

[Quorum sensing in Gram-negative bacteria: signal molecules, inhibitors and their potential therapeutic application]. / Zjawisko Quorum Sensing bakterii Gram-ujemnych: czasteczki sygnalowe i inhibitory oraz ich potencjalne zastosowanie terapeutyczne.

Quorum Sensing (QS) is a phenomenon of chemical cell-to-cell communication consisting in the synthesis and secretion of signal molecules called autoinducers into the environment, which contribute in regulation of various physiological processes. QS was identified in different bacterial species, including symbiotic and pathogenic bacteria. QS systems play a crucial role in regulation of expression of genes which control motility, biofilm formation, and synthesis of virulence factors by pathogenic bacteria. These systems recognize signal molecules of different specificity which belong to a few groups and enable intra- and interspecific communication of bacterial cells as well as communication with cells of eukaryotic organisms (hosts). Inhibition of QS called Quorum Quenching (QQ) is now regarded to be a promising strategy to combat bacterial infections. So far, a large group of substances of natural and synthetic origin with a function of QS inhibitors, which can have potential therapeutic applications, has been identified.

Mathematical Modelling of Bacterial Quorum Sensing: A Review.

Bacterial quorum sensing (QS) refers to the process of cell-to-cell bacterial communication enabled through the production and sensing of the local concentration of small molecules called autoinducers to regulate the production of gene products (e.g. enzymes or virulence factors). Through autoinducers, bacteria interact with individuals of the same species, other bacterial species, and with their host. Among QS-regulated processes mediated through autoinducers are aggregation, biofilm formation, bioluminescence, and sporulation. Autoinducers are therefore "master" regulators of bacterial lifestyles. For over 10 years, mathematical modelling of QS has sought, in parallel to experimental discoveries, to elucidate the mechanisms regulating this process. In this review, we present the progress in mathematical modelling of QS, highlighting the various theoretical approaches that have been used and discussing some of the insights that have emerged. Modelling of QS has benefited almost from the onset of the involvement of experimentalists, with many of the papers which we review, published in non-mathematical journals. This review therefore attempts to give a broad overview of the topic to the mathematical biology community, as well as the current modelling efforts and future challenges.

Compounds from Lactobacillus plantarum culture supernatants with potential pro-healing and anti-pathogenic properties in skin chronic wounds.

CONTEXT: It is necessary to advance the field of alternative treatments for chronic wounds that are financially accessible to the least economically developed countries. Previously we demonstrated that topical applications of Lactobacillus plantarum culture supernatants (LAPS) on human-infected chronic wounds reduce the pathogenic bioburden, the amount of necrotic tissue, and the wound area, as well as promote debridement, granulation tissue, and wound healing. OBJECTIVE: To study LAPS chemically and biologically and to find potential molecules responsible for its pro-healing and anti-pathogenic properties in chronic wounds. MATERIALS AND METHODS: (1) Chemical analysis: extracts were subjected to a column chromatography and the fractions obtained were studied by GCMS. (2) Quantification: dl-lactic acid (commercial kit), phenolic compounds (Folin-Ciocalteu), H2O2 (micro-titration), and cations (flame photometry). (3) Biological analysis: autoinducers type 2 (AI-2) (Vibrio harveyi BB170 bioassay), DNAase activity (Agar DNAase), and Pseudomonas aeruginosa biofilm inhibition (crystal violet technique). RESULTS: According to its biological activity, the most significant molecules found by GCMS were the following: antimicrobials (mevalonolactone, 5-methyl-hydantoine, benzoic acid, etc.); surfactants (di-palmitin, distearin, and 1,5-monolinolein); anesthetics (barbituric acid derivatives), and AI-2 precursors (4,5-dihydroxy-2,3-pentanedione and 2-methyl-2,3,3,4-tetrahydroxytetrahydrofurane). Concentrations measured (µg/mL): DL-lactic acid (11.71 ± 1.53) and H2O2 (36 ± 2.0); phenolic compounds (485.2 ± 15.20); sodium (370 ± 17); potassium 920 ± 24); calcium (20 ± 4); and magnesium (15 ± 3). DNAase from LAPS had activity on genomic DNA from PMNs and P. aeruginosa. DISCUSSION AND CONCLUSION: The molecules and biological activities found in LAPS could explain the observed effects in human chronic wounds.

Quorum regulated latent environmental cells of toxigenic Vibrio cholerae and their role in cholera outbreaks.

BACKGROUND: Diverse bacterial group behaviors are controlled by quorum sensing, a regulatory network of bacterial gene expression based on cell density, and involving communication through chemical signal molecules called autoinducers. Multidisciplinary research in toxigenic Vibrio cholerae the etiologic agent of cholera, appear to suggest group behavior in the ecology, epidemiology, pathogenesis and transmission of the pathogen. This review summarizes latest advances and known aspects of quorum regulated environmental survival form of V. cholerae, and their role in cholera outbreaks, as well as the significance of this knowledge in tracking the pathogen for prevention of cholera. MAIN BODY: Pathogenic V. cholerae naturally exists in aquatic reservoirs, and infects humans, often leading to epidemic outbreaks of cholera. Effective detection and monitoring of the pathogen in surface waters have been a research focus in preventing cholera outbreaks. However, in the aquatic reservoirs, V. cholerae persists mostly in a quiescent state referred to as viable but non-culturable (VBNC), or conditionally viable environmental cells (CVEC), which fail to grow in routine bacteriological culture. The presence of CVEC can, however, be observed by fluorescent antibody based microscopy, and they appear as clumps of cells embedded in an exopolysaccharide matrix. Current studies suggest that CVEC found in water are derived from in-vivo formed biofilms excreted by cholera patients. The transition to CVEC occurs when dilution of autoinducers in water blocks quorum-mediated regulatory responses that would normally disperse the cellular aggregates. Consequently, CVEC are resuscitated to actively growing cells if autoinducers are replenished, either in the laboratory, or naturally by other environmental bacteria or the intestinal microbiota when CVEC are ingested by humans or aquatic animals. CONCLUSION: Quorum sensing plays a crucial role in the environmental persistence of toxigenic V. cholerae in a latent state, and their periodic emergence to cause cholera outbreaks. Furthermore, the autoinducer driven resuscitation of these cells may be a basis for improving the detection of V. cholerae in water samples, and monitoring V. cholerae in their aquatic reservoirs in cholera endemic areas.

- Invited Review - Chemical signalling within the rumen microbiome.

Ruminants possess a specialized four-compartment forestomach, consisting of the reticulum, rumen, omasum, and abomasum. The rumen, the primary fermentative chamber, harbours a dynamic ecosystem comprising bacteria, protozoa, fungi, archaea, and bacteriophages. These microorganisms engage in diverse ecological interactions within the rumen microbiome, primarily benefiting the host animal by deriving energy from plant material breakdown. These interactions encompass symbiosis, such as mutualism and commensalism, as well as parasitism, predation, and competition. These ecological interactions are dependent on many factors, including the production of diverse molecules, such as those involved in quorum sensing (QS). QS is a density-dependent signalling mechanism involving the release of autoinducer (AIs) compounds, when cell density increases AIs bind to receptors causing the altered expression of certain genes. These AIs are classified as mainly being N-acyl-homoserine lactones (AHL; commonly used by Gram-negative bacteria) or autoinducer-2 based systems (AI-2; used by Gram-positive and Gram-negative bacteria); although other less common AI systems exist. Most of our understanding of QS at a gene-level comes from pure culture in vitro studies using bacterial pathogens, with much being unknown on a commensal bacterial and ecosystem level, especially in the context of the rumen microbiome. A small number of studies have explored QS in the rumen using 'omic' technologies, revealing a prevalence of AI-2 QS systems among rumen bacteria. Nevertheless, the implications of these signalling systems on gene regulation, rumen ecology, and ruminant characteristics are largely uncharted territory. Metatranscriptome data tracking the colonization of perennial ryegrass by rumen microbes suggest that these chemicals may influence transitions in bacterial diversity during colonization. The likelihood of undiscovered chemicals within the rumen microbial arsenal is high, with the identified chemicals representing only the tip of the iceberg. A comprehensive grasp of rumen microbial chemical signalling is crucial for addressing the challenges of food security and climate targets.