Search Results (96)

Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as a “superbug”, and its resistance mechanisms, including target modification, drug inactivation, efflux pumps, biofilm formation, and quorum sensing. The limitations of conventional antibiotics (e.g., β-lactams, vancomycin, macrolides) are discussed, alongside the promise of algal-derived compounds such as fatty acids, pigments, polysaccharides, terpenoids, and phenolic compounds. These metabolites exhibit potent anti-MRSA activity by disrupting cell division (via FtsZ inhibition), destabilizing membranes, and inhibiting protein synthesis and metabolic pathways, effectively countering multiple resistance mechanisms. Leveraging advances in algal biotechnology, this review highlights the untapped potential of marine algae to drive innovative, sustainable therapeutic strategies against antibiotic resistance. 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 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 search for probiotics to help limit antibiotic resistance is a major scientific challenge. The exploration of Lactobacillus postbiotics represents a promising approach to prevent pathogen invasion. With this aim, Limosilactobacillus fermentum Lf53, with a broad-spectrum of antagonistic activity, was characterized as a candidate probiotic strain with promising transit tolerance and broad spectrum of activity. A study on growth and postbiotic production in modified MRS broth with different carbohydrates and its vegan variant was carried out. This study presents a comprehensive approach to characterizing the anti-virulence properties of postbiotics derived from Lf53. The promising antibacterial, antibiofilm, and anti-quorum sensing activities of the cell-free supernatants (CFS) were assessed as part of the probiotic’s barrier mechanisms. Biofilm inhibition of P. aeruginosa revealed remarkable suppressive effects exerted by the three tested postbiotics, two of which (nCFS and aCFS) exhibited over 50% inhibition and more than 60% for lysates. The postbiotics’ influence on the production of violacein and pyocyanin pigments of Chromobacterium violaceum and Pseudomonas aeruginosa, which are markers for quorum sensing, highlighted their potential in regulating pathogenic mechanisms. The Lf53 lysates showed the most significant inhibition of violacein production across multiple assays, showing 29.8% reduction. Regarding pyocyanin suppression, the postbiotics also demonstrated strong activity. These are the first reported data on complex postbiotics (metabiotics and parabiotics) demonstrating their potential as anti-virulence agents to help combat pathogens associated with antibiotic-resistant infections. Full article

Aquatic products play a crucial role in meeting the increasing global demands for high-quality proteins. However, the occurrence of bacterial diseases results in significant economic losses worldwide. Aeromonas hydrophila (A. hydrophila) is the pathogen of several fish diseases. Antibiotics were widely used in combating bacterial diseases in aquaculture. The increasing occurrences of antibiotic resistance necessitate the restricted use of antibiotics. Consequently, developing drugs that avoid antibiotic resistance is important for the future of aquaculture. Quorum sensing (QS) is critical for bacterial pathogens in regulating bacterial virulence and is a promising target for developing anti-infective agents. Here, we found that turmeric oil with a MIC of 256 μg/mL could dose-dependently reduce the virulence phenotypes regulated by QS, ranging from 8 to 64 μg/mL, suggesting that sub-inhibitory concentrations of turmeric oil could inhibit bacterial virulence. Further qPCR findings demonstrated that turmeric oil could significantly inhibit the transcription of aerA, ahyI, and ahyR by a 54-fold, 36-fold, and 56-fold change reduction, respectively. Cell live/dead staining and animal study results showed that turmeric oil could inhibit the pathogenicity of A. hydrophila. Fish treated with turmeric oil showed a reduced mortality rate of 60%, whereas all fish in the positive control group died. Moreover, treatment with turmeric oil could alleviate the renal injury. Collectively, the results suggested that targeting bacterial virulence might be a useful approach to combating bacterial infections, and turmeric oil could serve as a potential agent for combating A. hydrophila infections. Full article

Untapped bioactive compounds from microbial endophytes offer a promising solution to counter antimicrobial and chemotherapeutic drug resistance when complexed as silver nanoparticles (AgNPs). AgNPs were biosynthesized using cell-free supernatants from endophytic Streptomyces sp. KE4D and Bacillus safensis KE4K isolated from the Kenyan medicinal plant Teclea nobilis, following fermentation in three different media. Bacterial extracts were analyzed using gas chromatography–mass spectrometry. AgNPs were characterized using Fourier-transform infrared spectroscopy and high-resolution transmission electron microscopy. Antimicrobial activity was assessed using agar well diffusion assays, and quorum sensing inhibition (QSI) was investigated using Chromobacterium violaceum. Anti-cancer potential was evaluated against breast (MCF-7) and prostate cancer (DU-145) cell lines using MTT assays. AgNPs were 5–55 nm in size, with KE4D AgNPs being spherical and KE4K AgNPs exhibiting various shapes. Cyclopropane acetic acids and fatty acids were identified as possible capping agents. Medium-dependent antimicrobial activity was observed, with medium Mannitol and medium 5294 AgNPs displaying stronger activity, particularly against Gram-negative indicators. KE4D medium 5294 AgNPs demonstrated 85.12% violacein inhibition at 140 µg/mL and better QSI activity, whilst KE4K AgNPs were better antimicrobials. The AgNPs IC₅₀ values were <3.5 µg/mL for MCF-7 and <2.5 µg/mL for DU-145 cells. The bioactivity of biosynthesized AgNPs is influenced by the bacterial isolate and fermentation medium, suggesting that AgNP synthesis can be tailored for specific bioactivity. Full article

Quorum sensing, a bacterial cell-to-cell communication mechanism, plays a key role in bacterial virulence and biofilm formation. Targeting quorum-sensing pathways represents a promising strategy for the development of novel antibacterial agents. This study evaluated the anti-quorum-sensing activities of 18 natural compounds, including cannabinoids, arylbenzofurans, flavonoids, caffeine, and chlorogenic acid, using the luminescent biosensor strain Vibrio harveyi MM30. V. harveyi MM30, a mutant strain deficient in the production of autoinducer-2 (AI-2) but responsive to exogenous AI-2, was used to assess the activity of test compounds on the AI-2 receptor pathway. Test compounds were incubated in AI-2-containing media, and luminescence was measured to evaluate quorum-sensing inhibition. Comparisons were made in the absence of AI-2 to determine AI-2-independent inhibitory activity. The most active compounds were further tested on methicillin-resistant Staphylococcus aureus (MRSA 7112) to determine their effects on AI-2 production in spent media. Among the tested compounds, the non-prenylated arylbenzofuran moracin M and the prenylated arylbenzofuran moracin C exhibited significant quorum-sensing inhibitory activity in the AI-2-mediated pathway. None of the test compounds significantly inhibited quorum sensing in the absence of AI-2. Five compounds (cannabigerol, cannabidiol, cannabigerolic acid, moracin M, and moracin C) were selected for further investigation in MRSA 7112 cultures. The spent media from MRSA 7112 cultures treated with moracin M (16, 32, 64 µg/mL) and cannabigerolic acid (16 µg/mL) showed significant inhibition of AI-2 production when transferred to V. harveyi MM30 cultures. Moracin M and cannabigerolic acid demonstrated potential as quorum-sensing inhibitors by targeting AI-2 production and signalling pathways in MRSA 7112 and V. harveyi. These findings suggest their potential for further development as antibacterial agents targeting quorum-sensing mechanisms. Full article

In recent years, plant essential oils have been confirmed as natural inhibitors of foodborne pathogens. Citrus reticulata Blanco cv. Tankan peel essential oil (CPEO) showed anti-Listeria monocytogenes (LM) activities, and this study investigated the associated mechanisms by using high-resolution electron microscope, fluorescence spectrometer, flow cytometer, potentiometer, and transcriptome sequencing. The results showed that CPEO restrained LM growth at a minimum inhibitory concentration of 2% (v/v). The anti-LM abilities of CPEO were achieved by disrupting the permeability of the cell wall, damaging the permeability, fluidity, and integrity of the cell membrane, disturbing the membrane hydrophobic core, and destroying the membrane protein conformation. Moreover, CPEO could significantly inhibit the LM aggregation from forming biofilm by reducing the extracellular polymeric substances’ (protein, polysaccharide, and eDNA) production and bacterial surface charge numbers. The RNA sequencing data indicated that LM genes involved in cell wall and membrane biosynthesis, DNA replication and repair, quorum sensing and two-component systems were expressed differently after CPEO treatment. These results suggested that CPEO could be used as a novel anti-LM agent and green preservative in the food sector. Further studies are needed to verify the anti-LM activities of CPEO in real food. 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 a harmful pathogen that causes a variety of acute and chronic infections through quorum sensing (QS) mechanisms. The increasing resistance of this bacterium to numerous antibiotics has created a demand for new medications that specifically target QS. Endophytes can be the source of compounds with antibacterial properties. This research is the first to examine tannic acid (TA) produced by endophytic fungus as a potential biotherapeutic agent. A novel endophytic fungal isolate identified as Penicillium oxalicum was derived from the cladodes of Opuntia ficus-indica (L.). The species identification for this isolate was confirmed through sequencing of the internal transcribed spacer region. The metabolites from the culture of this isolate were extracted using ethyl acetate, then separated and characterized using chromatographic methods. This led to the acquisition of TA, a compound that shows strong anti-QS and excellent antibacterial effects against extensively drug-resistant P. aeruginosa strains. Furthermore, it was shown that treating P. aeruginosa with the obtained TA reduced the secretion of virulence factors controlled by QS in a dose-dependent manner, indicating that TA inhibited the QS characteristics of P. aeruginosa. Simultaneously, TA significantly inhibited the expression of genes associated with QS, including rhlR/I, lasR/I, and pqsR. In addition, in silico virtual molecular docking showed that TA could efficiently bind to QS receptor proteins. Our results showed that P. oxalicum could be a new source of TA for the treatment of infections caused by extensively drug-resistant P. aeruginosa. Full article

Quorum sensing (QS) is a bacterial cell-to-cell communication mechanism that plays an essential role in bacterial pathogenesis. QS governs bacterial behavior and controls biofilm formation, which in turn contributes to antibiotic resistance. Therefore, identifying and synthesizing novel compounds to overcome QS and inhibit biofilm formation are essential. Coumarins are important plant-derived natural products with wide-ranging bioactivities and extensive applications, including antibacterial, antifungal, anticoagulant, antioxidant, anticancer, and anti-inflammatory properties. Additionally, coumarins are capable of QS rewiring and biofilm formation inhibition, leading to higher susceptibility to antimicrobial agents and less antibiotic resistance. Therefore, in this review, we aim to provide an overview of QS and biofilm formation. This review also discusses the role of natural and synthesized coumarins in controlling QS, inhibiting biofilm formation, and inducing synergy in antibiotic–coumarin combinations. Hence, this review emphasizes the potential of coumarin compounds to act as antibacterial agents and demonstrates their ability to alleviate antibiotic resistance. Full article

Lactic acid bacteria (LAB) are the most common probiotics, and they present excellent inhibitory effects on pathogenic bacteria. This study aimed to explore the anti-biofilm potential of the purified active substance of Lactiplantibacillus plantarum, named Z102-E. The effects of Z102-E on Listeria monocytogenes were investigated in detail, and a transcriptomic analysis was conducted to reveal the anti-biofilm mechanism. The results indicated that the sub-MIC of Z102-E (3.2, 1.6, and 0.8 mg/mL) decreased the bacterial growth and effectively reduced the self-aggregation, surface hydrophobicity, sugar utilization, motility, biofilm formation, AI-2 signal molecule, contents of extracellular polysaccharides, and extracellular protein of L. monocytogenes. Moreover, the inverted fluorescence microscopy observation confirmed the anti-biofilm effect of Z102-E. The transcriptomic analysis indicated that 117 genes were up-regulated and 214 were down-regulated. Z102-E regulated the expressions of genes related to L. monocytogenes quorum sensing, biofilm formation, etc. These findings suggested that Z102-E has great application potential as a natural bacteriostatic agent. Full article

Antibiotic resistance is a critical public health issue. Among the multi-drug resistant microorganisms in question, Pseudomonas aeruginosa has been designated by the WHO as a priority threat. Its virulence is orchestrated through quorum sensing (QS). This sophisticated communication network relies on the release and perception of autoinducers acting as population density indicators. Therefore, the interest of a quorum silencing pharmacological approach has unfolded to quench bacterial pathogenicity without impairing growth. In this article, we reported the development of a family of indazole–quinolone hybrids as anti-virulence agents. These new biaromatic compounds were designed as potential specific QS quenchers against P. aeruginosa. Our transdisciplinary research methodology included their synthesis using palladocatalyzed cross-coupling reactions, as well as their in silico physicochemical and in vitro biological evaluation. The hit 7-chloro-2-indazolyl-4-quinolone Ie shows a promising anti-biofilm and anti-pyocyanin efficiency (35% inhibition at 25 µM and 35% inhibition at 100 µM, respectively) without an anti-pseudomonal bacteriostatic effect. It also demonstrated a moderate eukaryotic cytotoxicity. Its anti-QS properties have been investigated using metabolomic and molecular modelling studies. Full article

The formation of microbial biofilm is a self-organizing process among bacterial cells, regulated by quorum-sensing (QS) mechanisms, contributing to development of infections. These processes, either separately or in combination, significantly contribute to bacterial resistance to antibiotics and disinfectants. A novel approach to addressing the challenge of treating infections due to antibacterial resistance involves the use of plant metabolites. In recent years, there has been increasing recognition of different phytochemicals as potential modulators. In our study, we evaluated the synergistic effect of chloroform and methanol extracts from Inula species against key virulence factors, including biofilm formation, violacein production, and swarming motility. Each of the 11 examined plant extracts demonstrated the ability to reduce biofilms and pigment synthesis in C. violaceum. Two of the extracts from I. britannica exhibited significant anti-biofilm and anti-quorum-sensing effects with over 80% inhibition. Their inhibitory effect on violacein synthesis indicates their potential as anti-QS agents, likely attributed to their high concentration of terpenoids (triterpenoids, sesquiterpene lactones, and diterpenoids). Scanning electron microscopy revealed a notable reduction in biofilm biomass, along with changes in biofilm architecture and cell morphology. Additionally, fluorescence microscopy revealed the presence of metabolically inactive cells, indicating the potent activity of the extracts during treatment. These new findings underscore the effectiveness of the plant extracts from the genus Inula as potential anti-virulent agents against C. violaceum. They also propose a promising strategy for preventing or treating its biofilm formation. Full article

The development of antibiotic-resistant microorganisms is a major global health concern. Recently, there has been an increasing interest in antimicrobial peptides as a therapeutic option. This study aimed to evaluate the triple-action (broad-spectrum antibacterial, anti-biofilm, and anti-quorum sensing activities) of melittin, a membrane-active peptide present in bee venom. The minimum inhibitory concentration and minimum bactericidal concentration of the melittin were determined using the microdilution method and agar plate counting. Growth curve analysis revealed that melittin showed a concentration-dependent antibacterial activity. Scanning electron microscope analysis revealed that melittin treatment altered the morphology. Confocal laser scanning microscope revealed that melittin increased the membrane permeability and intracellular ROS generation in bacteria, all of which contribute to bacterial cell death. In addition, the crystal violet (CV) assay was used to test the anti-biofilm activity. The CV assay demonstrated that melittin inhibited biofilm formation and eradicated mature biofilms. Biofilm formation mediated by quorum sensing (QS) plays a major role in this regard, so molecular docking and molecular dynamics analysis confirmed that melittin interacts with LasR receptors through hydrogen bonds, and further evaluates the anti-QS activity of melittin through the production of virulence factors (pyocyanin, elastase, and rhamnolipid), exopolysaccharides secretion, and bacterial motility, that may be the key to inhibiting the biofilm formation mechanism. The present findings highlight the promising role of melittin as a broad-spectrum antibacterial, anti-biofilm agent, and potential QS inhibitor, providing a new perspective and theoretical basis for the development of alternative antibiotics. Full article