Search Results (150)

This study elucidates how the quorum-sensing (QS) signal 3OC12-HSL exacerbates enterotoxigenic E. coli (ETEC) pathogenicity and intestinal barrier dysfunction. In vitro, 3OC12-HSL enhanced ETEC C83902 growth (66.7% CFU increase at 8 h) and dysregulated stress/growth genes (e.g., eight-fold rmf upregulation under static conditions). In synthetic gut microbiota, 3OC12-HSL selectively augmented E. coli colonization (37.6% 16S rDNA increase at 12 h). Murine studies revealed 3OC12-HSL reduced jejunal villus height (381.5 μm vs. 543.2 μm in controls), elevated serum LPS, D-lactate, and DAO, and altered microbial composition (Firmicutes/Bacteroidetes imbalance). The lactonase AiiA reversed these effects by degrading 3OC12-HSL. It abrogated bacterial growth stimulation (in vitro CFU restored to baseline), normalized microbiota diversity (Shannon index recovered to control levels), suppressed pro-inflammatory cytokines (IL-6/TNF-α reduction), and restored intestinal integrity (villus length: 472.5 μm, 20.5% increase vs. ETEC-infected mice). Our findings establish AiiA as a potent quorum-quenching agent that counteracts ETEC virulence via targeted signal inactivation, highlighting its translational value. Full article

Quorum quenching (QQ) is of interest for potential application as a sustainable strategy for bacterial disease control via communication interruption. The QQ enzyme can be used as a good alternative antagonist to combat antibiotic abuse and bacterial resistance. Here, genomic DNA sequencing was performed on N-acyl homoserine lactonase from the deep-sea strain Bacillus velezensis DH82 with Cluster of Orthologous Groups of proteins (COGs) annotation. The homologous sequences with β-lactamase domain-containing protein were predicted to be potential QQ enzymes and were cloned and expressed to study their quorum quenching properties by comparing them with the reported enzyme AiiA_3DHB. The experimental results of enzyme activity analysis and steady-state kinetics, as well as enzyme structure and substrate docking simulations and predictions, all consistently demonstrated that YtnP_DH82 presented superior enzyme structural stability and higher degradation efficiency of N-acyl homoserine lactones than AiiA_DH82 under the effects of pH, and temperature, and performed better on short -chain and 3-O-substituted AHSLs. The findings revealed the structural and biochemical characterization of YtnP_DH82 from the deep sea, which provide the capacity for further application in sustainable aquaculture as an alternative to antibiotics. Full article

Biofilm-associated infections caused by Gram-negative bacteria, especially multidrug-resistant strains, frequently occur in intensive care units and represent a major therapeutic challenge. The economic burden of biofilm-associated infections is considerable, making the search for new treatment approaches a focal point for policymakers and scientific funding bodies. Biofilm formation is regulated by quorum sensing (QS), a population density-dependent communication mechanism between cells mediated by small diffusible signaling molecules. QS modulates various intracellular processes, and some features of QS are common to all Gram-negative bacteria. While there are differences in the QS regulatory networks of different Gram-negative bacterial species, a common feature of most Gram-negative bacteria is the ability of N-acylhomoserine lactones (AHL) as inducers to diffuse across the bacterial membrane and interact with receptors located either in the cytoplasm or on the inner membrane. Targeting QS by inhibiting the synthesis, transport, or perception of signaling molecules using small molecules, quorum quenching enzymes, antibodies, combinatorial therapies, or nanoparticles is a promising strategy to combat virulence. In-depth knowledge of biofilm biology, antibiotic susceptibility, and penetration mechanisms, as well as a deep understanding of anti-QS agents, will contribute to the development of antimicrobial therapies to combat biofilm infections. Advancing antimicrobial therapies against biofilm infections requires a deep understanding of biofilm biology, antibiotic susceptibility, penetration mechanisms, and anti-QS strategies. This can be achieved through in vivo and clinical studies, supported by state-of-the-art tools such as machine learning and artificial intelligence. Full article

The quorum-quenching activity of essential oils (EOs) from Corsican aromatic plants was evaluated using the marine bacterium Aliivibrio fischeri as a model system. Among the eleven EOs screened, Myrtus communis EO showed significant interference with QS-regulated phenotypes (swimming motility, bioluminescence, and biofilm formation). Its activity was compared to Origanum vulgaris EO, known for its high carvacrol content and potent QS inhibition. The fractionation of M. communis EO revealed that its most polar fractions exhibited comparable levels of QS-disrupting activity. These chromatographic fractions significantly affected QS-controlled traits, indicating that minor or less volatile compounds may contribute to, or enhance, the overall bioactivity. Furthermore, M. communis EO and its polar fractions displayed stronger anti-QS effects against A. fischeri than O. vulgaris EO. These results highlight M. communis EO as a promising source of natural QS inhibitors and underscore the importance of exploring both complete EOs and their active fractions. This study supports the valorization of Mediterranean endemic flora as a reservoir of bioactive compounds, tested on a model system A. fischeri, and encourages future research on the potential of Myrtus communis against clinical bacterial isolates and the development of novel anti-virulence strategies. Full article

Xylella fastidiosa (Xf) is a xylem-limited Gram-negative phytopathogen responsible for severe plant diseases globally. Colonization and dissemination on host plants are regulated primarily by diffusible signal factors (DSFs) and quorum sensing (QS) molecules regulating biofilm formation, motility, and virulence factor synthesis. DSFs play a critical role in the transition of bacteria from adhesion to dispersal phases, influencing plant infection and transmission by vector. Because of Xf’s host range (over 550 plant species), effective containment strategies are highly demanded. In this review, we discuss the molecular mechanism of DSF-mediated signalling in Xf, especially concerning its role in pathogenicity and adaptation. Moreover, we shed light on innovative approaches to manage Xf, including quorum-quenching (QQ) strategies and transgenic plants targeted to disrupt QS pathways. Improved knowledge of DSF interactions with host plants and bacterial communities could provide an entry point for novel, sustainable disease control strategies to decrease Xf’s agricultural and ecological impact. Full article

The escalating global health crisis of antibiotic resistance, driven by the rapid emergence of multidrug-resistant (MDR) bacterial pathogens, necessitates urgent and innovative countermeasures. This review comprehensively examines the diverse mechanisms employed by bacteria to evade antibiotic action, including alterations in cell membrane permeability, efflux pump overexpression, biofilm formation, target site modifications, and the enzymatic degradation of antibiotics. Specific focus is given to membrane transport systems such as ATP-binding cassette (ABC) transporters, resistance–nodulation–division (RND) efflux pumps, major facilitator superfamily (MFS) transporters, multidrug and toxic compound extrusion (MATE) systems, small multidrug resistance (SMR) families, and proteobacterial antimicrobial compound efflux (PACE) families. Additionally, the review explores the global burden of MDR pathogens and evaluates emerging therapeutic strategies, including quorum quenching (QQ), probiotics, postbiotics, synbiotics, antimicrobial peptides (AMPs), stem cell applications, immunotherapy, antibacterial photodynamic therapy (aPDT), and bacteriophage. Furthermore, this review discusses novel antimicrobial agents, such as animal-venom-derived compounds and nanobiotics, as promising alternatives to conventional antibiotics. The interplay between clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) in bacterial adaptive immunity is analyzed, revealing opportunities for targeted genetic interventions. By synthesizing current advancements and emerging strategies, this review underscores the necessity of interdisciplinary collaboration among biomedical scientists, researchers, and the pharmaceutical industry to drive the development of novel antibacterial agents. Ultimately, this comprehensive analysis provides a roadmap for future research, emphasizing the urgent need for sustainable and cooperative approaches to combat antibiotic resistance and safeguard global health. Full article

This study aimed to isolate AHL-degrading bacteria from the intestine of Penaeus vannamei and evaluate their ability to control pathogenic Vibrio harveyi in P. vannamei larvae. Twenty-seven isolates were obtained from the digestive tract of healthy Pacific white shrimp juveniles (P. vannamei) after six cycles of pasteurization at 70 °C, but only three isolates (E₁LP₂, E₂LP₁, and E₂LP₂) could degrade AHL. The 16S sequence results gave a high identity (>95%) with Bacillus sp. The isolates exhibited quorum-quenching abilities by degrading AHLs, thereby disrupting Vibrio quorum sensing and virulence. In Zoea and Mysis, the challenged larvae plus the administration of E₁LP₂ resulted in the lowest survival compared to the other groups. Isolates degrading N-acyl homoserine lactone improved the survival of shrimp Zoea and Mysis larvae when challenged with pathogenic V. harveyi. This is the first report on the use of quorum-sensing disrupter bacteria in P. vannamei larval shrimp culture. Our findings suggest that these Bacillus spp. strains have potential as biocontrol agents for sustainable shrimp aquaculture, reducing the reliance on antibiotics while mitigating vibriosis outbreaks. Full article

Quorum sensing (QS) is a molecular communication mechanism among bacterial cells. It is critical in regulating virulence factors, motility, antibiotic resistance, and biofilm formation. Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen linked to healthcare-associated infections, food poisoning, and biofilm formation. Treating infections caused by pathogenic bacteria has become a challenge due to the development of multi-antibiotic resistance upon continuous exposure of bacteria to antibiotics. An alternative strategy to conventional antimicrobials to decrease the bacterial pathogenicity is QS inhibition, also known as quorum quenching. Using plant-derived compounds is an environmentally friendly strategy to block the bacterial QS and inhibit bacterial growth. Portulaca oleracea is a popular plant in different countries and is also used in traditional medicine. It is widely consumed raw in salads and as garnishes, though it can be cooked as a vegetarian dish. This study evaluates the antimicrobial activity of the methanolic extract of P. oleracea and its effectiveness in blocking or attenuating the QS of P. aeruginosa. The agar well diffusion method used for screening the antibacterial activity showed a significant growth inhibition of P. aeruginosa by the extract at 500 mg/mL with a minimum inhibitory concentration of 31.25 mg/mL. A bioindicator bacterium, Chromobacterium violaceum CV026, was used to determine the effect of the methanolic extract on the QS of P. aeruginosa. The results indicated a significant reduction in biofilm formation, pyocyanin production, and LasA staphylolytic activity. The phytochemical analysis by Gas Chromatography–Mass Spectrometry showed that the methanolic extract contained several phenols, alkaloids, esters, and other compounds previously reported to have antibacterial and antioxidant effects. These findings highlight the effectiveness of P. oleracea methanolic extract in attenuating the QS and virulence factors of P. aeruginosa. This study suggests that P. oleracea is an important source of natural antimicrobials and its use would be beneficial in food and pharmaceutical applications. Full article

Indwelling medical devices, such as urinary catheters, often experience bacterial colonization, forming biofilms that resist antibiotics and the host’s immune defenses through quorum sensing (QS), a chemical communication system. This study explores the development of antimicrobial coatings by immobilizing acylase, a quorum-quenching enzyme, on sandblasted polydimethylsiloxane (PDMS) surfaces. PDMS, commonly used in medical devices, was sandblasted to increase its surface roughness, enhancing acylase attachment. FTIR analysis confirmed that acylase retained its three-dimensional structure upon immobilization, preserving its enzymatic activity. The antibacterial efficacy of the coatings was tested against Pseudomonas aeruginosa (P. aeruginosa) (a common biofilm-forming pathogen), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli). The results showed that sandblasted PDMS surfaces had improved bacterial adhesion due to increased focal adhesion points, but acylase-functionalized surfaces had significantly reduced bacterial attachment and biofilm formation. Notably, the coatings inhibited P. aeruginosa growth by 40% under static conditions, demonstrating the potential of acylase-functionalized PDMS for medical applications. This approach offers a promising strategy for creating antimicrobial surfaces that prevent biofilm-related infections in urinary catheters and other medical devices. The findings highlight the dual role of surface roughness in enhancing enzyme attachment while reducing bacterial adhesion through effective QS inhibition. Full article

Biofilms are complex, highly organized structures formed by microorganisms, with functional cell arrangements that allow for intricate communication. Severe clinical challenges occur when anaerobic bacterial species establish long-lasting infections, especially those involving biofilms. These infections can occur in device-related settings (e.g., implants) as well as in non-device-related conditions (e.g., inflammatory bowel disease). Within biofilms, bacterial cells communicate by producing and detecting extracellular signals, particularly through specific small signaling molecules known as autoinducers. These quorum-sensing signals are crucial in all steps of biofilm formation: initial adhesion, maturation, and dispersion, triggering gene expression that coordinates bacterial virulence factors, stimulates immune responses in host tissues, and contributes to antibiotic resistance development. Within anaerobic biofilms, bacteria communicate via quorum-sensing molecules such as N-Acyl homoserine lactones (AHLs), autoinducer-2 (AI-2), and antimicrobial molecules (autoinducing peptides, AIPs). To effectively combat pathogenic biofilms, understanding biofilm formation mechanisms and bacterial interactions is essential. The strategy to disrupt quorum sensing, termed quorum quenching, involves methods like inactivating or enzymatically degrading signaling molecules, competing with signaling molecules for binding sites, or noncompetitively binding to receptors, and blocking signal transduction pathways. In this review, we comprehensively analyzed the fundamental molecular mechanisms of quorum sensing in biofilms formed by anaerobic bacteria. We also highlight quorum quenching as a promising strategy to manage bacterial infections associated with anaerobic bacterial biofilms. Full article

The prevalence of multidrug resistance (MDR) and stagnant drug-development pipelines have led to the rapid rise of hard-to-treat antibiotic-resistant bacterial infections. These infectious diseases are no longer just nosocomial but are also becoming community-acquired. The spread of MDR has reached a crisis level that needs immediate attention. The landmark O’Neill report projects that by 2050, mortality rates associated with MDR bacterial infections will surpass mortality rates associated with individuals afflicted with cancer. Since conventional antimicrobials are no longer very reliable, it is of great importance to investigate different strategies to combat these life-threatening infectious diseases. Here, we provide an overview of recent advances in viable alternative treatment strategies mainly targeting a pathogen’s virulence capability rather than viability. Topics include small molecule and immune inhibition of virulence factors, quorum sensing (QS) quenching, inhibition of biofilm development, bacteriophage-mediated therapy, and manipulation of an individual’s macroflora to combat MDR bacterial infections. Full article

The excessive use of biocides has considerable environmental and economic impacts; this is why new technologies have been sought to decrease the concentration levels applied in an effort to reduce the use of these substances. Microencapsulation using cyclodextrins has been widely used in the food and pharmaceutical industries as a way of reducing the concentrations of the active substance necessary to achieve a biological effect and/or eliminate its irritating or toxicological effects. In this study, the inclusion complexation behavior and binding ability of benzothiazolinone (BIT) with different β-cyclodextrins (β-CD, HP-β-CD, and Me-β-CD) was investigated. The intermolecular interactions were examined through UV and FTIR spectroscopy, DSC, 1D ¹H NMR, and 2D ROESY. The highest stability constant was observed for the BIT/Me-β-CD inclusion complex (299.5 ± 2.9 M⁻¹). Antibacterial activity was investigated against Staphylococcus aureus and Escherichia coli, and the results revealed that the BIT/Me-β-CD inclusion complex displays a higher antibacterial activity than BIT. The acute toxicity of the biocide and inclusion complex was also examined using the photobacterium Aliivibrio fischeri. Although BIT exhibited higher toxicity than the inclusion complex, further investigation is needed due to the quorum quenching effect of β-CDs. The data found suggest that BIT microencapsulation can increase its aqueous solubility and can be used as an effective tool to improve its chemical, biological, and ecotoxicological properties. Full article

The increase in antibiotic-resistant bacteria presents a significant risk to worldwide public health, emphasizing the necessity of novel approaches to address infections. Quorum sensing, an essential method of communication among bacteria, controls activities like the formation of biofilms, the production of virulence factors, and the synthesis of secondary metabolites according to the number of individuals in the population. Quorum quenching, which interferes with these processes, emerges as a vital approach to diminish bacterial virulence and prevent biofilm formation. Nanocarriers, characterized by their small size, high surface-area-to-volume ratio, and modifiable surface chemistry, offer a versatile platform for the disruption of bacterial communication by targeting various stages within the quorum sensing pathway. These features allow nanocarriers to infiltrate biofilms, disrupt cell membranes, and inhibit bacterial proliferation, presenting a promising alternative to traditional antibiotics. Integrating nanocarrier-based systems into combination therapies provides a multi-pronged approach to infection control, enhancing both the efficacy and specificity of treatment regimens. Nonetheless, challenges related to the stability, safety, and clinical effectiveness of nanomaterial-based antimicrobial treatments remain. Continued research and development are essential to overcoming these obstacles and fully harnessing the potential of nano-antimicrobial therapies. This review emphasizes the importance of quorum sensing in bacterial behavior and highlights the transformative potential of nanotechnology in advancing antimicrobial treatments, offering innovative solutions to combat antibiotic-resistant pathogens. Full article

Antibiotic resistance is a major problem and a major global health concern. In total, there are 16 million deaths yearly from infectious diseases, and at least 65% of infectious diseases are caused by microbial communities that proliferate through the formation of biofilms. Antibiotic overuse has resulted in the evolution of multidrug-resistant (MDR) microbial strains. As a result, there is now much more interest in non-antibiotic therapies for bacterial infections. Among these revolutionary, non-traditional medications is quorum sensing inhibitors (QSIs). Bacterial cell-to-cell communication is known as quorum sensing (QS), and it is mediated by tiny diffusible signaling molecules known as autoinducers (AIs). QS is dependent on the density of the bacterial population. QS is used by Gram-negative and Gram-positive bacteria to control a wide range of processes; in both scenarios, QS entails the synthesis, identification, and reaction to signaling chemicals, also known as auto-inducers. Since the usual processes regulated by QS are the expression of virulence factors and the creation of biofilms, QS is being investigated as an alternative solution to antibiotic resistance. Consequently, the use of QS-inhibiting agents, such as QSIs and quorum quenching (QQ) enzymes, to interfere with QS seems like a good strategy to prevent bacterial infections. This review sheds light on QS inhibition strategy and mechanisms and discusses how using this approach can aid in winning the battle against resistant bacteria. 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