Search Results (123)

With 80% of bacterial infections occurring as biofilms, biofilm-related infections have evolved into a critical public health concern. Probiotics such as Bacillus licheniformis have emerged as promising alternatives, offering new avenues for effective treatment. This study aimed to evaluate the activity of licheniformis against the growth, biofilm formation, motility, and quorum sensing (QS) of Salmonella typhimurium. Several experiments were conducted: The minimum inhibitory concentration (MIC) of Bacillus licheniformis against Salmonella typhimurium was determined to be 0.5 mg/mL using the broth microdilution method. The inhibition zone of 100 mg/mL of B. licheniformis against Salmonella typhimurium was 19.98 ± 1.38 mm; the time-growth curve showed that B. licheniformis can effectively inhibit the growth of Salmonella typhimurium. In biofilm experiments, at the MIC of B. licheniformis, the inhibition rate of immature biofilm of Salmonella typhimurium was 86.9%, and it significantly reduced the production of biofilm components (EPS, e-DNA, and extracellular proteases) (p < 0.05). The disruption rate of mature biofilm by B. licheniformis at the MIC was 66.89%, and it significantly decreased the levels of biofilm components (EPS and e-DNA) (p < 0.5). Microscopic observation showed that both the MIC and 1/2 MIC of B. licheniformis could reduce the number of bacteria in the Salmonella typhimurium biofilm, which was not conducive to the formation and maintenance of the biofilm structure. Swimming/Swarming assays and QS experiments confirmed that B. licheniformis inhibits the motility of Salmonella typhimurium and the secretion of AI-1-type quorum sensing molecules and downregulates the AI-2 quorum sensing system by upregulating lsr gene expression. These findings suggest that B. licheniformis could be a potential antimicrobial agent and biofilm inhibitor. Full article

The growing threat of antibiotic-resistant Gram-negative bacteria highlights the urgent need for innovative, non-bactericidal therapeutic strategies. Quorum-sensing (QS) inhibition has emerged as a promising approach to attenuate bacterial virulence without exerting selective pressure. This study evaluated the antimicrobial, anti-QS, and antibiofilm properties of aqueous extracts from five medicinal plants native to northeastern Mexico: Gymnosperma glutinosum, Ibervillea sonorae, Larrea tridentata, Olea europaea, and Tecoma stans. Disk diffusion and violacein quantification assays using Chromobacterium violaceum demonstrated significant QS inhibition by G. glutinosum and T. stans, with violacein reductions of 60.02% and 52.72%, respectively, at 40 mg/mL. While L. tridentata and O. europaea exhibited antibacterial activity, I. sonorae showed no growth or pigment inhibition but achieved the highest biofilm disruption (89.89%) against Salmonella typhimurium. UPLC-MS analysis identified chlorogenic acid, kaempferol, and D-(−)-quinic acid as major constituents, compounds previously associated with QS modulation. These findings highlight the potential of traditional Mexican plant species as sources of QS inhibitors and bio-film-disrupting agents, supporting their further development as alternatives to conventional antibiotics. 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

This study investigated the mechanism by which N-acyl-homoserine lactone (AHL) signaling molecules influence ammonia-oxidizing microorganisms (AOMs) under inhibitory conditions. In laboratory-scale sequential batch reactors (SBRs), the effects of different AHLs (C6-HSL and C8-HSL) on the metabolic activity, microbial community structure, and quorum sensing (QS) system response of AOMs were examined. Caffeic acid, 1-octyne, and allylthiourea were used as ammoxidation inhibitors. The results indicated that under inhibitory conditions, AHLs effectively reduced the loss of ammonia oxidation activity and enhanced the resistance of AOMs to unfavorable environments. Additionally, AHLs enriched AOMs in the microbial community, wherein C6-HSL significantly increased the abundance of amoA genes in AOMs. Furthermore, AHLs maintained the activity of QS-related genes and preserved the communication ability between microorganisms. Correlation analysis revealed a positive relationship between AOMs and QS functional bacteria, suggesting that AHLs can effectively regulate the ammonia oxidation process. Overall, exogenous AHLs can improve the metabolic activity and competitive survival of AOMs under inhibitory conditions. Full article

As the antibiotic resistance of pathogens becomes increasingly severe, it is becoming more feasible to use methods that suppress the virulence of pathogens rather than exerting selective pressure on their growth. Pseudomonas aeruginosa, a dangerous opportunistic pathogen, infects hosts by producing multiple virulence factors, which are regulated by quorum-sensing (QS) systems, including the las systems, rhl systems, and pqs systems. This study used the chromosome lacZ transcription fusion reporter model to screen the traditional Chinese medicine monomer library and found that bakuchiol can effectively inhibit the pqs system and related virulence phenotypes of P. aeruginosa, including the production of virulence factors (pyocyanin, hydrogen cyanide, elastase, and lectin) and motility (swarming, swimming, and twitching motility) without affecting its growth. Subsequently, through genetic complementation analysis, we found that bakuchiol inhibited the function of the transcriptional activation protein PqsR of the pqs system in P. aeruginosa in a concentration-dependent manner. Furthermore, molecular dynamics simulation study results indicated that bakuchiol can target PqsR of the pqs system, thereby inhibiting the pqs system. Among the amino acids in PqsR, ALA-168 may be a key amino acid residue in the hydrophobic interaction between PqsR protein and bakuchiol. Finally, in vivo experiments demonstrated that bakuchiol attenuated the pathogenicity of P. aeruginosa to Chinese cabbage (Brassica pekinensis) and Caenorhabditis elegans. In summary, this study suggests that bakuchiol is an effective inhibitor that targets the pqs system of P. aeruginosa, providing a new strategy for addressing P. aeruginosa infections. Full article

Background/Objectives: The present work aimed to compare the effects of the standardized dry extract from the leaves of Monteverdia ilicifolia, popularly known as “espinheira-santa”, with omeprazole in the management of dyspepsia related to gastroesophageal reflux disease (GERD). Methods: A double-blind, randomized, non-inferiority and double-dummy clinical trial was conducted. In total, 86 patients with GERD symptoms were randomized into three groups: Omeprazol (20 mg), M. ilicifolia (400 mg), or M. ilicifolia (860 mg). Capsules were provided by SUSTENTEC^®, Pato Bragato, Brazil. It was requested that the participants take three capsules before breakfast and dinner for 4 weeks. Clinical outcomes were obtained at the beginning and end of the study, with GERD symptoms (QS-GERD), the impact of heartburn symptoms on quality of life (HBQOL), and medical records. Results: Overall, 75.6% of the participants showed adherence without any differences among the experimental groups. All groups had significant reductions in both QS-GERD and HBQOL scores. Omeprazole and 400 and 860 mg of M. ilicifolia decreased the QS-GERD total scores at the endpoint compared to the baseline (Chi-square = 129.808; p < 0.0001), as well as individual item scores, such as heartburn intensity (Chi-square = 93.568, p < 0.0001) and heartburn after meals (Chi-square = 126.426, p < 0.0001). There were no differences among the experimental groups after the intervention. Conclusions: Our results suggest that capsules with a standardized dry extract from the leaves of M. ilicifolia at a dosage of 400 or 860 mg are non-inferior to omeprazole, a proton pump inhibitor. Full article

Bacterial quorum sensing (QS) is a critical communication process that regulates gene expression in response to population density, influencing activities such as biofilm formation, virulence, and antibiotic resistance. This study investigates the inhibitory effects of five phytochemicals—apigenin, carnosol, chlorogenic acid, quercetin, and rosmarinic acid—on the S-ribosylhomocysteinase (LuxS) enzyme, a key player in AI-2 signaling across both Gram-positive and Gram-negative bacteria. Using molecular docking studies, we identified that these phytochemicals interact with the LuxS enzyme, with apigenin, carnosol, chlorogenic acid, and rosmarinic acid binding within the substrate-binding pocket and exhibiting binding scores below −7.0 kcal/mol. Subsequent in vitro assays demonstrated that these compounds inhibited AI-2 signaling and biofilm formation in Escherichia coli MG1655 in a concentration-dependent manner. Notably, carnosol and chlorogenic acid showed the most potent effects, with IC₅₀ values of approximately 60 μM. These findings suggest that these phytochemicals may serve as potential QS inhibitors, providing a foundation for developing new anti-pathogenic agents to combat bacterial infections without promoting antibiotic resistance. Further studies are warranted to explore the therapeutic applications of these compounds in both clinical and agricultural settings. Full article

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that remains a prevalent clinical and environmental challenge. Quorum-sensing (QS) molecules are effective biomarkers in pinpointing the presence of P. aeruginosa. This study aimed to develop a convenient-to-use, whole-cell biosensor using P. aeruginosa reporters individually encapsulated within alginate-poly-L-lysine (alginate-PLL) microbeads to specifically detect the presence of bacterial autoinducers. The PLL-reinforced microbeads were prepared using a two-step method involving ionic cross-linking and subsequent coating with thin layers of PLL. The alginate-PLL beads showed good stability in the presence of a known cation scavenger (sodium citrate), which typically limits the widespread applications of calcium alginate. In media containing synthetic autoinducers—such as N-(3-oxo dodecanoyl) homoserine lactone (3-oxo-C₁₂-HSL) and N-butanoyl-L-homoserine lactone (C₄-HSL), or the cell-free supernatants of planktonic or the flow-cell biofilm effluent of wild P. aeruginosa (PAO1)—the encapsulated bacteria enabled a dose-dependent detection of the presence of these QS molecules. The prepared bioreporter beads remained stable during prolonged storage at 4 and −80 °C and were ready for on-the-spot sensing without the need for recovery. The proof-of-concept, optical fiber-based, and whole-cell biosensor developed here demonstrates the practicality of the encapsulated bioreporter for bacterial detection based on specific QS molecules. 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

With the widespread phenomenon of antibiotic resistance and the diffusion of multiple drug-resistant bacterial strains, enormous efforts are being conducted to identify suitable alternative agents against pathogenic microorganisms. Since an association between biofilm formation and antibiotic resistance phenotype has been observed, a promising strategy pursued in recent years focuses on controlling and preventing this formation by targeting and inhibiting the Quorum Sensing (QS) system, whose central role in biofilm has been extensively demonstrated. Therefore, the research and development of Quorum Quenching (QQ) compounds, which inhibit QS, has gradually attracted the attention of researchers and has become a new strategy for controlling harmful microorganisms. Among these, a number of both natural and synthetic compounds have been progressively identified as able to interrupt the intercellular communication within a microbial community and the adhesion to a surface, thus disintegrating mature/preformed biofilms. This review describes the role played by QS in the formation of bacterial biofilms and then focuses on the mechanisms of different natural and synthetic QS inhibitors (QSIs) exhibiting promising antibiofilm ability against Gram-positive and Gram-negative bacterial pathogens and on their applications as biocontrol strategies in various fields. Full article

Biofilms play a decisive role in the infectious process and the development of antibiotic resistance. The establishment of bacterial biofilms is regulated by a signal-mediated cell–cell communication process called “quorum sensing” (QS). The identification of quorum sensing inhibitors (QSI) to mitigate the QS process may facilitate the development of novel treatment strategies for biofilm-based infections. In this study, the traditional medicinal plant Ocimum sanctum was screened for QS inhibitory potential. Sub-MICs of the extract significantly affected the secretion of EPS in Gram-negative human pathogens such as Escherichia coli, Pseudomonas aeruginosa PAO1, Proteus mirabilis, and Serratia marcescens, as well as aquaculture pathogens Vibrio harveyi, V. parahaemolyticus, and V. vulnificus, which render the bacteria more sensitive, leading to a loss of bacterial biomass from the substratum. The observed inhibitory activity of the O. sanctum extract might be attributed to the presence of eugenol, as evidenced through ultraviolet (UV)-visible, gas chromatography-mass spectroscopy (GC–MS), Fourier transformer infrared (FTIR) spectroscopy analyses, and computational studies. Additionally, the QSI potential of eugenol was corroborated through in vitro studies using the marker strain Chromobacterium violaceum. Full article

Pseudomonas aeruginosa is an opportunistic pathogen that usually causes chronic infections and even death in patients. The treatment of P. aeruginosa infection has become more challenging due to the prevalence of antibiotic resistance and the slow pace of new antibiotic development. Therefore, it is essential to explore non-antibiotic methods. A new strategy involves screening for drugs that target the quorum-sensing (QS) system. The QS system regulates the infection and drug resistance in P. aeruginosa. In this study, veratryl alcohol (VA) was found as an effective QS inhibitor (QSI). It effectively suppressed the expression of QS-related genes and the subsequent production of virulence factors under the control of QS including elastase, protease, pyocyanin and rhamnolipid at sub-inhibitory concentrations. In addition, motility activity and biofilm formation, which were correlated with the infection of P. aeruginosa, were also suppressed by VA. In vivo experiments demonstrated that VA could weaken the pathogenicity of P. aeruginosa in Chinese cabbage, Drosophila melanogaster, and Caenorhabditis elegans infection models. Molecular docking, combined with QS quintuple mutant infection analysis, identified that the mechanism of VA could target the LasR protein of the las system mainly. Moreover, VA increased the susceptibility of P. aeruginosa to conventional antibiotics of tobramycin, kanamycin and gentamicin. The results firstly demonstrate that VA is a promising QSI to treat infections caused by P. aeruginosa. Full article

Due to the resistance of Gram-negative bacteria Pseudomonas aeruginosa PAO1 to most clinically relevant antimicrobials, the use of traditional antibiotic treatments in hospitals is challenging. The formation of biofilms, which is regulated by the quorum-sensing (QS) system of Pseudomonas aeruginosa (PA), is an important cause of drug resistance. There are three main QS systems in P. aeruginosa: the las system, the rhl system, and the pqs system. The inhibitors of the las system are the most studied. Previously, the compound AOZ-1 was found to have a certain inhibitory effect on the las system when screened. In this study, twenty-four compounds were designed and synthesized by modifying the Linker and Rings of AOZ-1. Using C. violaceum CV026 as a reporter strain, this study first assessed the inhibitory effects of new compounds against QS, and their SAR was investigated. Then, based on the SAR analysis of compound AOZ-1 derivatives, the parent core of AOZ-1 was replaced to explore the structural diversity. Then, nine new compounds were designed and synthesized with a new nucleus core component of 3-amino-tetrahydro-l,3-oxazin-2-one. The compound Y-31 (IC₅₀ = 91.55 ± 3.35 µM) was found to inhibit the QS of C. violaceum CV026. Its inhibitory effect on C. violaceum CV026 was better than that of compound AOZ-1 (IC₅₀ > 200 µM). Furthermore, biofilm formation is one of the important causes of Pseudomonas aeruginosa PAO1 resistance. In this study, it was found that compound Y-31, with a new nucleus core component of 3-amino-tetrahydro-l,3-oxazin-2-one, had the highest biofilm inhibition rate (40.44%). The compound Y-31 has a certain inhibitory effect on the production of PAO1 virulence factors (pyocyanin, rhamnolipid, and elastase) and swarming. When the concentration of compound Y-31 was 162.5 µM, the inhibition rates of pyocyanin, rhamnolipid, and elastase were 22.48%, 6.13%, and 22.67%, respectively. In vivo, the lifetime of wildtype Caenorhabditis elegans N2 infected with P. aeruginosa PAO1 was markedly extended by the new parent nucleus Y-31. This study also performed cytotoxicity experiments and in vivo pharmacokinetics experiments on the compound Y-31. In conclusion, this study identified a compound, Y-31, with a new nucleus core component of 3-amino-tetrahydro-l,3-oxazin-2-one, which is a potential agent for treating P. aeruginosa PAO1 that is resistant to antibiotics and offers a way to discover novel antibacterial medications. Full article

An ethyl acetate extract of a marine actinomycete strain, Nocardiopsis mentallicus SCSIO 53858, isolated from a deep-sea sediment sample in the South China Sea, exhibited anti-quorum-sensing (QS) activity against Chromobacterium violaceum CV026. Guided by the anti-QS activity, a novel active compound was isolated and purified from the extract and was identified as 2,3-dimethoxycinnamic acid (2,3-DCA) through spectral data analysis. At a concentration of 150 μg/mL, 2,3-DCA exhibited robust inhibitory effects on three QS-regulated traits of C. violaceum CV026: violacein production, swarming motility, and biofilm formation, with inhibition rates of 73.9%, 65.9%, and 37.8%, respectively. The quantitative reverse transcription polymerase chain reaction results indicated that 2,3-DCA can disrupt the QS system in C. violaceum CV026 by effectively suppressing the expression of QS-related genes, including cviR, vioA, vioB, and vioE. Molecular docking analysis revealed that 2,3-DCA hinders the QS system by competitively binding to the same binding pocket on the CviR receptor as the natural signal molecule N-hexanoyl-L-homoserine lactone. Collectively, these findings suggest that 2,3-DCA exhibits promising potential as an inhibitor of QS systems, providing a potential solution to the emerging problem of bacterial resistance. Full article