Search Results (12)

Bacterial blight in rice, caused by Xanthomonas oryzae pv. oryzae (Xoo), poses a serious threat to global rice production. The ability of Xoo to form biofilms is a key factor for its virulence. The OryR protein is a LuxR-type quorum-sensing regulator essential for biofilm formation and Xoo pathogenicity. However, the three-dimensional structure of OryR remains poorly understood. This study integrates homology modeling, molecular dynamics (MD) simulations, and virtual screening to elucidate the structure of OryR and identify potential inhibitors that target its ligand-binding domain. MD simulations confirmed the structural stability of OryR, and comparative analysis with experimentally determined structures of ligand- or inhibitor-bound homologs revealed a binding site in OryR with a distinct hourglass-like shape for long-range contacts. Virtual screening of over 200,000 compounds from four chemical libraries identified several promising inhibitor candidates, with the top compounds showing strong binding energies in both molecular mechanics-generalized Born surface area (−68.3 kcal/mol) and molecular mechanics Poisson–Boltzmann surface area (−19.3 kcal/mol) calculations. Overall, this study provides insights into the OryR structure and highlights potential inhibitors that can be developed as novel agents to control bacterial blight. However, additional experimental validations are required to refine and optimize these leads for drug development. Full article

Unlike sucrose, sucralose is a non-cariogenic artificial sweetener, commonly included in dental care products such as chewing gums, toothpastes, and mouth rinses to enhance palatability for consumers. While its non-cariogenic action is well established, there is limited evidence regarding the potential anti-cariogenic mechanisms of sucralose. This study investigated whether sucralose interferes with QS involved in oral bacterial biofilm formation. A representative LuxR-type QS regulator, LasR, was expressed in the presence of sucralose and/or its native ligand, N-acyl homoserine lactone (AHL). The expressed protein was purified using nickel-affinity chromatography and quantified by the Bradford assay. The findings reveal that sucralose significantly inhibits AHL-dependent signaling, presumably by disrupting receptor–ligand interactions. These results provide insights into a possible molecular mechanism underlying the anti-cariogenic action of sucralose, highlighting its potential as a functional additive in oral health formulations. Full article

Quorum sensing (QS) is a mechanism by which bacteria detect and respond to cell density, regulating collective behaviors. Burkholderia plantarii, the causal agent of rice seedling blight, employs the LuxIR-type QS system, common among Gram-negative bacteria, where LuxI-type synthase produces QS signals recognized by LuxR-type regulators to control gene expression. This study aimed to elucidate the QS mechanism in B. plantarii KACC18965. Through whole-genome analysis and autoinducer assays, the plaI gene, responsible for QS signal production, was identified. Motility assays confirmed that C8-homoserine lactone (C8-HSL) serves as the QS signal. Physiological experiments revealed that the QS-defective mutant exhibited reduced virulence, impaired swarming motility, and delayed biofilm formation compared to the wild type. Additionally, the QS mutant demonstrated weakened antibacterial activity against Escherichia coli and decreased phosphate solubilization. These findings indicate that QS in B. plantarii significantly influences various pathogenicity and survival traits, including motility, biofilm formation, antibacterial activity, and nutrient acquisition, highlighting the critical role of QS in pathogen virulence and adaptability. Full article

Microcystis-dominated cyanobacterial blooms (MCBs) frequently occur in freshwaters worldwide due to massive Microcystis colony formation and severely threaten human and ecosystem health. Quorum sensing (QS) is a direct cause of Microcystis colony formation that drives MCBs outbreak by regulating Microcystis population characteristics and behaviors. Many novel findings regarding the fundamental knowledge of the Microcystis QS phenomenon and the signaling molecules have been documented. However, little effort has been devoted to comprehensively summarizing and discussing the research progress and exploration directions of QS signaling molecules-mediated QS system in Microcystis. This review summarizes the action process of N-acyl homoserine lactones (AHLs) as major signaling molecules in Microcystis and discusses the detailed roles of AHL-mediated QS system in cellular morphology, physiological adaptability, and cell aggregation for colony formation to strengthen ecological adaptability and competitive advantage of Microcystis. The research progress on QS mechanisms in Microcystis are also summarized. Compared to other QS systems, the LuxI/LuxR-type QS system is more likely to be found in Microcystis. Also, we introduce quorum quenching (QQ), a QS-blocking process in Microcystis, to emphasize its potential as QS inhibitors in MCBs control. Finally, in response to the research deficiencies and gaps in Microcystis QS, we propose several future research directions in this field. This review deepens the understanding on Microcystis QS knowledge and provide theoretical guidance in developing strategies to monitor, control, and harness MCBs. Full article

Hafnia alvei, a specific spoilage microorganism, has a strong capacity to destroy food protein and lead to spoilage. The aim of this study was to evaluate the phase-dependent regulation of lux-type genes on the spoilage characteristics of H. alvei H4. The auto-inducer synthase gene luxI and a regulatory gene luxR of the quorum sensing systems in H. alvei H4 were knocked out to construct the mutant phenotypes. On this basis, the research found that the luxI and luxR genes had a strong positive influence on not only flagella-dependent swimming ability and biofilm formation but also the production of putrescine and cadaverine. The luxR gene could downregulate putrescine production. The maximum accumulation of putrescine in wild type, ΔluxI, ΔluxR and ΔluxIR were detected at 24 h, reaching up to 695.23 mg/L, 683.02 mg/L, 776.30 mg/L and 724.12 mg/L, respectively. However, the luxI and luxR genes have a potential positive impact on the production of cadaverine. The maximum concentration of cadaverine produced by wild type, ΔluxI, ΔluxR and ΔluxIR were 252.7 mg/L, 194.5 mg/L, 175.1 mg/L and 154.2 mg/L at 72 h. Moreover, the self-organizing map analysis revealed the phase-dependent effects of two genes on spoilage properties. The luxI gene played a major role in the lag phase, while the luxR gene mainly acted in the exponential and stationary phases. Therefore, the paper provides valuable insights into the spoilage mechanisms of H. alvei H4. Full article

In bacteria, group-coordinated behavior such as biofilm formation or virulence are often mediated via cell–cell communication, a process referred to as quorum sensing (QS). The canonical QS system of Gram-negative bacteria uses N-acyl homoserine lactones (AHLs) as communication molecules, which are produced by LuxI-type synthases and sensed by cognate LuxR-type receptors. These receptors act as transcriptional regulators controlling the expression of specific genes. Some bacteria harbor LuxR-type receptors lacking a cognate LuxI-type synthases, designated as LuxR solos. Among many other LuxR solos, the entomopathogenic enteric bacterium Photorhabdus luminescens harbors a SdiA-like LuxR solo containing an AHL signal-binding domain, for which a respective signal molecule and target genes have not been identified yet. Here we performed SPR analysis to demonstrate that SdiA acts as a bidirectional regulator of transcription, tightly controlling its own expression and the adjacent PluDJC_01670 (aidA) gene in P. luminescens, a gene supposed to be involved in the colonization of eukaryotes. Via qPCR we could further determine that in sdiA deletion mutant strains, aidA is upregulated, indicating that SdiA negatively affects expression of aidA. Furthermore, the ΔsdiA deletion mutant exhibited differences in biofilm formation and motility compared with the wild-type. Finally, using nanoDSF analysis we could identify putative binding ability of SdiA towards diverse AHLs, but also to plant-derived signals, modulating the DNA-binding capacity of SdiA, suggesting that this LuxR solo acts as an important player in interkingdom signaling between P. luminescens and plants. Full article

Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum sensing (QS) to regulate cellular interactions via small chemical signaling molecules which also help with adaptation under undesirable survival conditions. Proteobacteria use acyl-homoserine lactone (AHL) molecules as autoinducers to sense population density and modulate gene expression. The LuxI-type enzymes synthesize AHL molecules, while the LuxR-type proteins (AHL transcriptional regulators) bind to AHLs to regulate QS-dependent gene expression. Diverse AHLs have been identified, and the diversity extends to AHL synthases and AHL receptors. This review comprehensively explains the molecular diversity of AHL signaling components of Pseudomonas aeruginosa, Chromobacterium violaceum, Agrobacterium tumefaciens, and Escherichia coli. The regulatory mechanism of AHL signaling is also highlighted in this review, which adds to the current understanding of AHL signaling in Gram-negative bacteria. We summarize molecular diversity among well-studied QS systems and recent advances in the role of QS proteins in bacterial cellular signaling pathways. This review describes AHL-dependent QS details in bacteria that can be employed to understand their features, improve environmental adaptation, and develop broad biomolecule-based biotechnological applications. Full article

Bacteria use a cell-cell communication process called quorum sensing (QS) to orchestrate collective behaviors. QS relies on the group-wide detection of extracellular signal molecules called autoinducers (AI). Quorum sensing is required for virulence and biofilm formation in the human pathogen Pseudomonas aeruginosa. In P. aeruginosa, LasR and RhlR are homologous LuxR-type soluble transcription factor receptors that bind their cognate AIs and activate the expression of genes encoding functions required for virulence and biofilm formation. While some bacterial signal transduction pathways follow a linear circuit, as phosphoryl groups are passed from one carrier protein to another ultimately resulting in up- or down-regulation of target genes, the QS system in P. aeruginosa is a dense network of receptors and regulators with interconnecting regulatory systems and outputs. Once activated, it is not understood how LasR and RhlR establish their signaling hierarchy, nor is it clear how these pathway connections are regulated, resulting in chronic infection. Here, we reviewed the mechanisms of QS progression as it relates to bacterial pathogenesis and antimicrobial resistance and tolerance. Full article

Members of the Sphingomonadales are renowned for their ability to degrade polycyclic aromatic hydrocarbons (PAHs). However, little is known about the regulatory mechanisms of the degradative pathway. Using cross-feeding bioassay, a functional LuxI/LuxR-type acyl-homoserine lactone (AHL)-mediated quorum sensing (QS) system was identified from Croceicoccus naphthovorans PQ-2, a member of the order Sphingomonadales. Inactivation of the QS system resulted in a significant decrease in PAHs degradation. The QS system positively controlled the expression of three PAH-degrading genes (ahdA1e, xylE and xylG) and a regulatory gene ardR, which are located on the large plasmid. Interestingly, the transcription levels of these three PAH-degrading genes were significantly down-regulated in the ardR mutant. In addition, bacterial cell surface hydrophobicity and cell morphology were altered in the QS-deficient mutant. Therefore, the QS system in strain PQ-2 positively regulates PAH degradation via two mechanisms: (i) by induction of PAH-degrading genes directly and/or indirectly; and (ii) by an increase of bacterial cell surface hydrophobicity. The findings of this study improve our understanding of how the QS system influences the degradation of PAHs, therefore facilitating the development of new strategies for the bioremediation of PAHs. Full article

Natural products play vital roles against infectious diseases since ancient times and most drugs in use today are derived from natural sources. Worldwide, multi-drug resistance becomes a massive threat to the society with increasing mortality. Hence, it is very crucial to identify alternate strategies to control these ‘super bugs’. Pseudomonas aeruginosa is an opportunistic pathogen reported to be resistant to a large number of critically important antibiotics. Quorum sensing (QS) is a cell–cell communication mechanism, regulates the biofilm formation and virulence factors that endow pathogenesis in various bacteria including P. aeruginosa. In this study, we identified and evaluated quorum sensing inhibitors (QSIs) from plant-based natural products against P. aeruginosa. In silico studies revealed that catechin-7-xyloside (C7X), sappanol and butein were capable of interacting with LasR, a LuxR-type quorum sensing regulator of P. aeruginosa. In vitro assays suggested that these QSIs significantly reduced the biofilm formation, pyocyanin, elastase, and rhamnolipid without influencing the growth. Especially, butein reduced the biofilm formation up to 72.45% at 100 µM concentration while C7X and sappanol inhibited the biofilm up to 66% and 54.26% respectively. Microscale thermophoresis analysis revealed that C7X had potential interaction with LasR (K_D = 933±369 nM) and thermal shift assay further confirmed the biomolecular interactions. These results suggested that QSIs are able to substantially obstruct the P. aeruginosa QS. Since LuxR-type transcriptional regulator homologues are present in numerous bacterial species, these QSIs may be developed as broad spectrum anti-infectives in the future. Full article

Quorum sensing (QS) is a bacterial cell-to-cell signaling mechanism that collectively regulates and synchronizes behaviors by means of small diffusible chemical molecules. In rhizobia, QS systems usually relies on the synthesis and detection of N-acyl-homoserine lactones (AHLs). In the model bacterium Sinorhizobium meliloti functions regulated by the QS systems TraI-TraR and SinI-SinR(-ExpR) include plasmid transfer, production of surface polysaccharides, motility, growth rate and nodulation. These systems are also present in other bacteria of the Sinorhizobium genus, with variations at the species and strain level. In Sinorhizobium fredii NGR234 phenotypes regulated by QS are plasmid transfer, growth rate, sedimentation, motility, biofilm formation, EPS production and copy number of the symbiotic plasmid (pSym). The analysis of the S. fredii HH103 genomes reveal also the presence of both QS systems. In this manuscript we characterized the QS systems of S. fredii HH103, determining that both TraI and SinI AHL-synthases proteins are responsible of the production of short- and long-chain AHLs, respectively, at very low and not physiological concentrations. Interestingly, the main HH103 luxR-type genes, expR and traR, are split into two ORFs, suggesting that in S. fredii HH103 the corresponding carboxy-terminal proteins, which contain the DNA-binding motives, may control target genes in an AHL-independent manner. The presence of a split traR gene is common in other S. fredii strains. Full article

The increasing threat of Acinetobacter baumannii as a nosocomial pathogen is mainly due to the occurrence of multidrug-resistant strains that are associated with the real problem of its eradication from hospital wards. The particular ability of this pathogen to form biofilms contributes to its persistence, increases antibiotic resistance, and promotes persistent/device-related infections. We previously demonstrated that virstatin, which is a small organic compound known to decrease virulence of Vibrio cholera via an inhibition of T4-pili expression, displayed very promising activity to prevent A. baumannii biofilm development. Here, we examined the antibiofilm activity of mono-unsaturated chain fatty acids, palmitoleic (PoA), and myristoleic (MoA) acids, presenting similar action on V. cholerae virulence. We demonstrated that PoA and MoA (at 0.02 mg/mL) were able to decrease A. baumannii ATCC 17978 biofilm formation up to 38% and 24%, respectively, presented a biofilm dispersing effect and drastically reduced motility. We highlighted that these fatty acids decreased the expression of the regulator abaR from the LuxIR-type quorum sensing (QS) communication system AbaIR and consequently reduced the N-acyl-homoserine lactone production (AHL). This effect can be countered by addition of exogenous AHLs. Besides, fatty acids may have additional non-targeted effects, independent from QS. Atomic force microscopy experiments probed indeed that PoA and MoA could also act on the initial adhesion process in modifying the material interface properties. Evaluation of fatty acids effect on 22 clinical isolates showed a strain-dependent antibiofilm activity, which was not correlated to hydrophobicity or pellicle formation ability of the tested strains, and suggested a real diversity in cell-to-cell communication systems involved in A. baumannii biofilm formation. Full article