Quorum-sensing Molecules Research Articles

Rhodopseudomonas palustris Quorum Sensing Molecule pC-HSL Induces Systemic Resistance to TMV Infection via Upregulation of NbSIPK/NbWIPK Expressions in Nicotiana benthamiana.

G-negative bacteria produce myriad N-acyl-homoserine lactones (AHLs) that can function as quorum sensing (QS) signaling molecules. AHLs are also known to regulate various plant biological activities. p-Coumaroyl-homoserine lactone (pC-HSL) is the only QS molecule produced by a photosynthetic bacterium, Rhodopseudomonas palustris. The role of pC-HSL in the interaction between R. palustris and plant has not been investigated. In this study, we investigated the effect of pC-HSL on plant immunity and found that this QS molecule can induce a systemic resistance to Tobacco mosaic virus (TMV) infection in Nicotiana benthamiana. The results show that pC-HSL treatment can prolong the activation of two mitogen-associated protein kinase genes (i.e., NbSIPK and NbWIPK) and increase the expression of transcription factor WRKY8 as well as immune response marker genes NbPR1 and NbPR10, leading to an increased accumulation of reactive oxygen species (ROS) in the TMV-infected plants. Our results also show that pC-HSL treatment can increase activities of two ROS-scavenging enzymes, peroxidase and superoxide dismutase. Knockdown of NbSIPK or NbWIPK expression in N. benthamiana plants through virus-induced gene silencing nullified or attenuated pC-HSL-induced systemic resistance, indicating that the functioning of pC-HSL relies on the activity of those two kinases. Meanwhile, pC-HSL-pretreated plants also showed a strong induction of kinase activities of NbSIPK and NbWIPK after TMV inoculation. Taken together, our results demonstrate that pC-HSL treatment increases plant resistance to TMV infection, which is helpful to uncover the outcome of interaction between R. palustris and its host plants.

Bitter taste receptor T2R14 detects quorum sensing molecules from cariogenic Streptococcus mutans and mediates innate immune responses in gingival epithelial cells.

Host-pathogen interactions play an important role in defining the outcome of a disease. Recent studies have shown that the bacterial quorum sensing molecules (QSM) can interact with host cell membrane proteins, mainly G protein-coupled receptors (GPCRs), and induce innate immune responses. However, few studies have examined QSM-GPCR interactions and their influence on oral innate immune responses. In this study, we examined the role of bitter taste receptor T2R14 in sensing competence stimulating peptides (CSPs) secreted by cariogenic bacterium Streptococcus mutans and in mediating innate immune responses in gingival epithelial cells (GECs). Transcriptomic and western blot analyses identify T2R14 to be highly expressed in GECs. Our data show that only CSP-1 from S. mutans induces robust intracellular calcium mobilization compared to CSP-2 and CSP-3. By using CRISPR-Cas9, we demonstrate that CSP-1 induced calcium signaling and secretion of cytokines CXCL-8/IL-8, TNF-α, and IL-6 is mediated through T2R14 in GECs. Interestingly, the NF-kB signaling activated by CSP-1 in GECs was independent of T2R14. CSP-1-primed GECs attracted differentiated HL-60 immune cells (dHL-60) and this effect was abolished in T2R14 knock down GECs and also in cells primed with T2R14 antagonist 6-Methoxyflavone (6-MF). Our findings identify S. mutans CSP-1 as a peptide ligand for the T2R family. Our study establishes a novel host-pathogen interaction between cariogenic S. mutans CSP-1 and T2R14 in GECs leading to an innate immune response. Collectively, these findings suggest T2Rs as potential therapeutic targets to modulate innate immune responses upon oral bacterial infections.

Bitter Taste Receptor as a Therapeutic Target in Orthopaedic Disorders.

Non-gustatory, extraoral bitter taste receptors (T2Rs) are G-protein coupled receptors that are expressed throughout the body and have various functional responses when stimulated by bitter agonists. Presently, T2Rs have been found to be expressed in osteoclasts and osteocytes where osteoclasts were capable of detecting bacterial quorum-sensing molecules through the T2R38 isoform. In the innate immune system, stimulating T2Rs induces anti-inflammatory and anti-pathogenic effects through the phospholipase C/inositol triphosphate pathway, which leads to intracellular calcium release from the endoplasmic reticulum. The immune cells with functional responses to T2R activation also play a role in bone inflammation and orthopaedic disorders. Furthermore, increasing intracellular calcium levels in bone cells through T2R activation can potentially influence bone formation and resorption. With recent studies finding T2R expression in bone cells, we examine the potential of targeting this receptor to treat bone inflammation and to promote bone anabolism.

Disproof of the Proposed Structures of Bradyoxetin, a Putative Bradyrhizobium japonicum Signaling Molecule, and HMCP, a Putative Ralstonia solanacearum Quorum-Sensing Molecule.

First, we revisited the reported NMR data of bradyoxetin, a putative cell density factor of Bradyrhizobium japonicum, and found some inconsistencies in the proposed structure. To elucidate the correct structure, we synthesized model oxetane compounds and confirmed that the NMR data of the synthetic compounds did not match those of the reported bradyoxetin. After reinterpreting the reported NMR data, we concluded that bradyoxetin must be chloramphenicol. Next, some derivatives of 2-hydroxy-4-((methylamino)(phenyl)methyl)cyclopentanone (HMCP), which is a putative quorum-sensing molecule of Ralstonia solanacearum, were synthesized. The NMR spectra of the synthesized compounds were completely different from those of the reported natural products. Based on theoretical studies, including the estimation of 1H and 13C NMR chemical shifts using density functional theory calculations, we confirmed the correctness of the structure of the synthesized compound. These results strongly suggest that the proposed structure of HMCP could be incorrect.

Characteristics of Treponema denticola lipooligosaccharide in presence of hemin and quorum-sensing molecule

ObjectivesThe study aimed to examine the diverse bioactivity of lipooligosaccharide extracted from T. denticola cultured in the presence of hemin and quorum-sensing inhibitor. DesignT. denticola was cultured in the presence or absence hemin or 2(5 H)-furanone, and lipooligosaccharide from T. denticola cultured in various conditions was extracted using an extraction kit. To investigate bioactivity of the lipooligosaccharide, human gingival fibroblasts (HGFs) were treated with the extracted lipooligosaccharide in the presence or absence of Tannerella forsythia lipopolysaccharide. The induction of cytokine expressions was investigated by real-time RT-PCR and ELISA, and the signaling pathway was examined by immunoblotting. To investigate antagonistic mechanisms of the lipooligosaccharide, HGFs were cotreated with fluorescence-labeled T. forsythia lipopolysaccharide and the extracted lipooligosaccharide. Binding of T. forsythia lipopolysaccharide to the cell was analyzed by a flow cytometer. ResultsLipooligosaccharide induced a low level of cytokine expression at high concentration of hemin or 2(5 H)-furanone. Lipooligosaccharide extracted from T. denticola cultured in higher concentration of hemin and 2(5 H)-furanone had a greater inhibitory effect on induction of cytokine expression by T. forsythia lipopolysaccharide. Further, lipooligosaccharide inhibited the activation of NF-κB and mitogen-activated protein kinase signaling pathways by T. forsythia lipopolysaccharide. Lipooligosaccharide inhibited the binding of T. forsythia lipopolysaccharide to HGFs in the presence of CD14 and LBP. ConclusionsThe characteristics of T. denticola lipooligosaccharide may be altered by bacterial communication and host factors.

Metabolic Exchange and Energetic Coupling between Nutritionally Stressed Bacterial Species: Role of Quorum-Sensing Molecules.

Formation of multispecies communities allows nearly every niche on earth to be colonized, and the exchange of molecular information among neighboring bacteria in such communities is key for bacterial success. To clarify the principles controlling interspecies interactions, we previously developed a coculture model with two anaerobic bacteria, Clostridium acetobutylicum (Gram positive) and Desulfovibrio vulgaris Hildenborough (Gram negative, sulfate reducing). Under conditions of nutritional stress for D. vulgaris, the existence of tight cell-cell interactions between the two bacteria induced emergent properties. Here, we show that the direct exchange of carbon metabolites produced by C. acetobutylicum allows D vulgaris to duplicate its DNA and to be energetically viable even without its substrates. We identify the molecular basis of the physical interactions and how autoinducer-2 (AI-2) molecules control the interactions and metabolite exchanges between C. acetobutylicum and D. vulgaris (or Escherichia coli and D. vulgaris). With nutrients, D. vulgaris produces a small molecule that inhibits in vitro the AI-2 activity and could act as an antagonist in vivo Sensing of AI-2 by D. vulgaris could induce formation of an intercellular structure that allows directly or indirectly metabolic exchange and energetic coupling between the two bacteria.IMPORTANCE Bacteria have usually been studied in single culture in rich media or under specific starvation conditions. However, in nature they coexist with other microorganisms and build an advanced society. The molecular bases of the interactions controlling this society are poorly understood. Use of a synthetic consortium and reducing complexity allow us to shed light on the bacterial communication at the molecular level. This study presents evidence that quorum-sensing molecule AI-2 allows physical and metabolic interactions in the synthetic consortium and provides new insights into the link between metabolism and bacterial communication.

Profiling of antimicrobial metabolites of plant growth promoting Pseudomonas spp. isolated from different plant hosts.

The online version contains supplementary material available at 10.1007/s13205-020-02585-8.

Deciphering bacterial social traits via diffusible signal factor (DSF) -mediated public goods in an anammox community

Both the benefits of bacterial quorum sensing (QS) and cross-feeding for bio-reactor performance in wastewater treatment have been recently reported. As the social traits of microbial communities, how bacterial QS regulating bacterial trade-off by cross-feeding remains unclear. Here, we find diffusion signal factor (DSF), a kind of QS molecules, can bridge bacterial interactions through regulating public goods (extracellular polymeric substances (EPS), amino acids) for metabolic cross-feedings. It showed that exogenous DSF-addition leads to change of public goods level and community structure dynamics in the anammox consortia. Approaches involving meta-omics clarified that anammox and a Lautropia-affiliated species in the phylum Proteobacteria can supply costly public goods for DSF-Secretor species via secondary messenger c-di-GMP regulator (Clp) after sensing DSF. Meanwhile, DSF-Secretor species help anammox bacteria scavenge extracellular detritus, which creates a more suitable environment for the anammox species, enhances the anammox activity, and improves the nitrogen removal rate of anammox reactor. The trade-off induces discrepant metabolic loads of different microbial clusters, which were responsible for the community succession. It illustrated the potential to artificially alleviate metabolic loads for certain bacteria. Deciphering microbial interactions via QS not only provides insights for understanding the social behavior of microbial community, but also creates new thought for enhancing treatment performance through regulating bacterial social traits via quorum sensing-mediated public goods.

Pharmacology of T2R Mediated Host-Microbe Interactions.

Bitter taste receptors (T2Rs) belong to the G protein-coupled receptor superfamily. Humans express 25 T2Rs that are known to detect several bitter compounds including bacterial quorum sensing molecules (QSM). Primarily found to be key receptors for bitter sensation T2Rs are known to play an important role in mediating innate immune responses in oral and extraoral tissues. Several studies have led to identification of Gram-negative and Gram-positive bacterial QSMs as agonists for T2Rs in airway epithelial cells and immune cells. However, the pharmacological characterization for many of the QSM-T2R interactions remains poorly defined. In this chapter, we discuss the extraoral roles including localization of T2Rs in extracellular vesicles, molecular pharmacology of QSM-T2R interactions, role of T2Rs in mediating innate immune responses, and some of the challenges in understanding T2R pharmacology.

In Vitro Effects of Farnesol Alone and in Combination with Antifungal Drugs Against Aspergillus Clinical Isolates.

Farnesol is an extracellular quorum-sensing molecule produced by Candida albicans. Farnesol is also a sesquiterpene alcohol existing in many herbal products and has various activity against fungal cells. We aimed to investigate the efficacy of farnesol alone and the contribution of farnesol on the activity of voriconazole and amphotericin B against Aspergillus clinical isolates in vitro. A total of 45 Aspergillus clinical isolates were used in this study. The MIC values of voriconazole, amphotericin B, and farnesol were determined using reference broth microdilution method. The interactions of farnesol with voriconazole and amphotericin B were investigated by the checkerboard method and evaluated based on the fractional inhibitor concentration index (FICI). The MIC ranges of farnesol, voriconazole, and amphotericin B were 1,500-6,000 μM, 0.125-1 μg/mL, and 0.125-0.5 μg/mL against Aspergillus fumigatus isolates, 3,000-12,000 μM, 0.125-0.5 μg/mL, and 0.25-2 μg/mL against Aspergillus flavus isolates, respectively. The most common interaction in combination tests was "no interaction," and synergistic interaction was not detected. The combinations of farnesol with voriconazole and amphotericin B had antagonistic activity against 38% and 27% of all isolates, respectively.We concluded that the responses of different fungal species against farnesol are variable, and different interactions may be observed when it is combined with different antifungals. Therefore, it should be noted that farnesol may have an adverse effect on some fungi or interact negatively with antifungals used in combination.

662. Identification of Clinically Relevant Microbes with the MasSpec Pen

BackgroundIn the age of antimicrobial resistance, rapid identification of infectious agents is critical for antimicrobial stewardship and effective therapy. To this end, ambient ionization mass spectrometry techniques have been applied for rapid identification of microbes directly from culture isolates. We have developed a handheld, mass spectrometry-based device, the MasSpec Pen, that permits direct molecular analysis of a biological sample in seconds (Scheme 1). Here, we employ the MasSpec Pen to identify clinically relevant microbes directly from culture isolates.Methods Staphylococcus aureus, Staphylococcus epidermidis, Group A and B Streptococcus, Kingella kingae (K.k), and Pseudomonas aeruginosa (P.a) were cultured on 5% sheep’s blood nutrient agar at 37 °C overnight. Colonies were transferred to a glass slide where they were analyzed directly with the MasSpec Pen coupled to a Q Exactive mass spectrometer (Thermo Scientific) in negative ion mode. For MasSpec Pen analysis, a 10 µL droplet of water was held in contact with the sample surface for 3 seconds and then aspirated to the mass spectrometer for analysis.Data was normalized and the molecular features resulting from the analysis solvent and nutrient medium were removed. The least absolute shrinkage and selection operator (lasso) statistical method was used to build classification models for prediction of bacterial identity. Model performance was evaluated by leave-one-out cross-validation and a validation set of samples.Scheme 1: MasSpec Pen workflow ResultsVarious small molecules were detected including metabolites and glycerophospholipid species. The mass spectral profiles for each species exhibited qualitative differences among them (Figure 1). Additionally, several quorum-sensing molecules were observed in P.a. including hydroxy-heptyl-quinoline (m/z 242.155).Lasso statistical classifiers were created to differentiate organisms at the level of Gram type, genus, and species with each model comprised of a sparse set of molecular features. Accuracies of 90% or greater were achieved for all lasso models and as high as 98% for the differentiation of Staphylococcus (Staph.) and Streptococcus (Strep.).Figure 1: Molecular profiles of species analyzed Figure 2: Statistical classification results ConclusionThese results demonstrate the potential of the MasSpec Pen as a tool for clinical analysis of infected biospecimens.DisclosuresSydney C. Povilaitis, BA, MS Pen Technologies, Inc. (Other Financial or Material Support, Patent) Livia Eberlin, PhD, MS Pen Technolpogies, Inc. (Board Member, Shareholder)

Biofilms.

In reality, most microorganisms are not free floating. They exist in biofilms, a community of many of them from the same species or from other genera and attached to surfaces.Microorganisms undergo a transition from free-floating, planktonic microorganisms to a sessile, surface-attached one. Contact with a surface induces changes in gene expression, and a strong attachment of microcolonies occurs only after a few hours. The maturation of a biofilm is associated with matrix formation. The matrix is of importance as it provides stability and protects against environmental insults, it consists of polysaccharides, water, lipids, proteins, and extracellular DNA. Biofilms can be found everywhere - in the environment, in water systems - and they play an important role in medicine and dentistry. In medicine, infections of chronic wounds, of the respiratory tract in cystic fibrosis infections, or when linked with incorporated biomaterial are mostly biofilm associated. In the oral cavity, the most prevalent oral diseases, dental caries, and periodontitis are multi-species biofilm-associated diseases. Although not acting alone, key pathogens drive the development of the microbial shift. Microorganisms metabolize sugar and create an acidic environment where aciduric bacteria (including mutans streptococci) become dominant, which leads to the demineralization of enamel and dentine. Porphyromonas gingivaliscauses biofilm dysbiosis in the development of periodontal disease. Biofilm-associated infections are extremely difficult to treat. The matrix serves as a barrier to antimicrobial agents and there are subpopulations of dormant bacteria resistant to antimicrobials requiring metabolically active cells. Approaches to treat biofilm-associated infections include the modification of the biofilm composition, inhibitors of quorum-sensing molecules, or interfering with matrix constituents.

The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3.

Serum paraoxonase-1 (PON1) is the most studied member of the group of paraoxonases (PONs). This enzyme possesses three enzymatic activities: lactonase, arylesterase, and paraoxonase activity. PON1 and its isoforms play an important role in drug metabolism as well as in the prevention of cardiovascular and neurodegenerative diseases. Although all three members of the PON family have the same origin and very similar amino acid sequences, they have different functions and are found in different locations. PONs exhibit substrate promiscuity, and their true physiological substrates are still not known. However, possible substrates include homocysteine thiolactone, an analogue of natural quorum-sensing molecules, and the recently discovered derivatives of arachidonic acid—bioactive δ-lactones. Directed evolution, site-directed mutagenesis, and kinetic studies provide comprehensive insights into the active site and catalytic mechanism of PON1. However, there is still a whole world of mystery waiting to be discovered, which would elucidate the substrate promiscuity of a group of enzymes that are so similar in their evolution and sequence yet so distinct in their function.

Antibiofilm and antifungal activities of medium-chain fatty acids against Candida albicans via mimicking of the quorum-sensing molecule farnesol.

Candida biofilms are tolerant to conventional antifungal therapeutics and the host immune system. The transition of yeast cells to hyphae is considered a key step in C. albicans biofilm development, and this transition is inhibited by the quorum-sensing molecule farnesol. We hypothesized that fatty acids mimicking farnesol might influence hyphal and biofilm formation by C. albicans. Among 31 saturated and unsaturated fatty acids, six medium-chain saturated fatty acids, that is, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid and lauric acid, effectively inhibited C. albicans biofilm formation by more than 75% at 2µgml-1 with MICs in the range 100-200µgml-1 . These six fatty acids at 2µgml-1 and farnesol at 100µgml-1 inhibited hyphal growth and cell aggregation. The addition of fatty acids to C. albicans cultures decreased the productions of farnesol and sterols. Furthermore, down-regulation of several hyphal and biofilm-related genes caused by heptanoic or nonanoic acid closely resembled the changes caused by farnesol. In addition, nonanoic acid, the most effective compound diminished C. albicans virulence in a Caenorhabditis elegans model. Our results suggest that medium-chain fatty acids inhibit more effectively hyphal growth and biofilm formation than farnesol.

Targeted and untargeted quantification of quorum sensing signalling molecules in bacterial cultures and biological samples via HPLC-TQ MS techniques

Quorum sensing (QS) is the ability of some bacteria to detect and to respond to population density through signalling molecules. QS molecules are involved in motility and cell aggregation mechanisms in diseases such as sepsis. Few biomarkers are currently available to diagnose sepsis, especially in high-risk conditions. The aim of this study was the development of new analytical methods based on liquid chromatography-mass spectrometry for the detection and quantification of QS signalling molecules, including N-acyl homoserine lactones (AHL) and hydroxyquinolones (HQ), in biofluids. Biological samples used in the study were Pseudomonas aeruginosa bacterial cultures and plasma from patients with sepsis. We developed two MS analytical methods, based on neutral loss (NL) and product ion (PI) experiments, to identify and characterize unknown AHL and HQ molecules. We then established a multiple-reaction-monitoring (MRM) method to quantify specific QS compounds. We validated the HPLC-MS-based approaches (MRM-NL-PI), and data were in accord with the validation guidelines. With the NL and PI MS-based methods, we identified and characterized 3 and 13 unknown AHL and HQ compounds, respectively, in biological samples. One of the newly found AHL molecules was C12-AHL, first quantified in Pseudomonas aeruginosa bacterial cultures. The MRM quantitation of analytes in plasma from patients with sepsis confirmed the analytical ability of MRM for the quantification of virulence factors during sepsis.Graphical abstract

Quorum sensing systems as a new target to prevent biofilm-related oral diseases.

The present study summarizes the current knowledge on the role of bacterial extracellular signaling systems, known as quorum sensing (QS), in oral biofilm formation, and on the possibility of blocking these microbial communication systems as a potential approach to prevent and treat oral infectious diseases. A detailed literature review of the current knowledge of QS in the oral cavity was performed, using the databases MEDLINE (through PubMed) and Web of Science. Accumulating direct and indirect evidence indicates an important role of QS molecules in the oral microbial ecosystem. The mechanisms regulating gene expression through bacterial communication systems constitute a promising target to control oral biofilm formation. Although cell-to-cell communication is pivotal for biofilm formation of many pathogenic bacteria, knowledge concerning microbial interactions and signaling processes within multispecies biofilms in the oral cavity is still limited.

The Evanescent GacS Signal.

The GacS histidine kinase is the membrane sensor of the major upstream two-component system of the regulatory Gac/Rsm signal transduction pathway. This pathway governs the expression of a wide range of genes in pseudomonads and controls bacterial fitness and motility, tolerance to stress, biofilm formation, and virulence or plant protection. Despite the importance of these roles, the ligands binding to the sensor domain of GacS remain unknown, and their identification is an exciting challenge in this domain. At high population densities, the GacS signal triggers a switch from primary to secondary metabolism and a change in bacterial lifestyle. It has been suggested, based on these observations, that the GacS signal is a marker of the emergence of nutritional stress and competition. Biochemical investigations have yet to characterize the GacS signal fully. However, they portray this cue as a low-molecular weight, relatively simple and moderately apolar metabolite possibly resembling, but nevertheless different, from the aliphatic organic acids acting as quorum-sensing signaling molecules in other Proteobacteria. Significant progress in the development of metabolomic tools and new databases dedicated to Pseudomonas metabolism should help to unlock some of the last remaining secrets of GacS induction, making it possible to control the Gac/Rsm pathway.

AHL-priming for enhanced resistance as a tool in sustainable agriculture.

Bacteria communicate with each other through quorum sensing (QS) molecules. N-acyl homoserine lactones (AHL) are one of the most extensively studied groups of QS molecules. The role of AHL molecules is not limited to interactions between bacteria; they also mediate inter-kingdom interaction with eukaryotes. The perception mechanism of AHL is well-known in bacteria and several proteins have been proposed as putative receptors in mammalian cells. However, not much is known about the perception of AHL in plants. Plants generally respond to short-chained AHL with modification in growth, while long-chained AHL induce AHL-priming for enhanced resistance. Since plants may host several AHL-producing bacteria and encounter multiple AHL at once, a coordinated response is required. The effect of the AHL combination showed relatively low impact on growth but enhanced resistance. Microbial consortium of bacterial strains that produce different AHL could therefore be an interesting approach in sustainable agriculture. Here, we review the molecular and genetical basis required for AHL perception. We highlight recent advances in the field of AHL-priming. We also discuss the recent discoveries on the impact of combination(s) of multiple AHL on crop plants and the possible use of this knowledge in sustainable agriculture.

Co-culture of Chlorella and Scenedesmus could enhance total lipid production under bacteria quorum sensing molecule stress

When coupling wastewater treatment and biofuel production, bacteria inevitably compete with microalgae for nutrients and habitat resources. Yet, microalgae utilize symbiotic relationships to mediate adverse effects in unfavorable environments. We hypothesized microalgal co-culture strategy could be a feasible approach to resist the quorum-sensing molecule stress from bacteria. Here, we used two model microalgae taxa, Chlorella and Scenedesmus, to compare cell growth and lipid production in mono- and co-culture conditions under the stress of a representative bacterial signal, C6-HSL. Co-culture cultivation reduced growth inhibition (by 50 % for Chlorella and 35 % for Scenedesmus) induced by C6-HSL. Antioxidant enzymes and mitochondrial activities were inhibited by C6-HSL stress in monoculture, but they were negligibly affected using the co-culture strategy. The maximum lipid productivity and production of the co-culture system were 0.12 g/(L d) and 0.71 g/L, respectively, and lipid production was 20–79 % higher than that of Chlorella and Scenedesmus monocultures. We found that the co-culture strategy could efficiently limit bacterial-induced competition stress and thus improve microalgae lipid production.

Bacterial chatter in chronic wound infections.

One of the hallmark characteristics of chronic diabetic wounds is the presence of biofilm-forming bacteria. Bacteria encapsulated in a biofilm may coexist as a polymicrobial community and communicate with each other through a phenomenon termed quorum sensing (QS). Here, we describe the QS circuits of bacterial species commonly found in chronic diabetic wounds. QS relies on diffusion of signaling molecules and the local concentration changes of these molecules that bacteria experience in wounds. These biochemical signaling pathways play a role not only in biofilm formation and virulence but also in wound healing. They are, therefore, key to understanding the distinctive nature of these infections. While several in vivo and in vitro models exist to study QS in wounds, there has been limited progress in understanding the interplay between QS molecules and host factors that contribute to wound healing. Lastly, we examine the potential of targeting QS for both diagnosis and therapeutic intervention purposes.