Search Results (295)

Nosocomial infections caused by ESKAPE pathogens represent a significant burden to global health. These pathogens may exhibit multidrug resistance (MDR) mechanisms, of which mechanisms such as efflux pumps and biofilm formation are gaining significant importance. Multidrug resistance mechanisms in ESKAPE pathogens have led to an increase in the effective costs in health care and a higher risk of mortality in hospitalized patients. These pathogens utilize antimicrobial efflux pump mechanisms and bacterial biofilm-forming capabilities to escape the bactericidal action of antimicrobials. ESKAPE bacteria forming colonies demonstrate increased expression of efflux pump-encoding genes. Efflux pumps not only expel antimicrobial agents but also contribute to biofilm formation by bacteria through (1) transport of molecules and transcription factors involved in biofilm quorum sensing, (2) bacterial fimbriae structure transport for biofilm adhesion to surfaces, and (3) regulation of a transmembrane gradient to survive the difficult conditions of biofilm microenvironments. The synergistic role of these mechanisms complicates treatment outcomes. Given the mechanistic link between biofilms and efflux pumps, therapeutic strategies should focus on targeting anti-biofilm mechanisms alongside efflux pump inactivation with efflux pump inhibitors. This review explores the molecular interplay between efflux pumps and biofilm formation, emphasizing potential therapeutic strategies such as efflux pump inhibitors (EPIs) and biofilm-targeting agents. Full article

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

Marine biofouling, the process of marine microorganisms, algae, and invertebrates attaching to and forming biofilms on ship hulls, underwater infrastructure, and marine equipment in ocean environments, severely impacts shipping and underwater operations by increasing fuel consumption, maintenance costs, and corrosion risks, and by threatening marine ecosystem stability via invasive species transport. This study reports the development of a hydrogel-metal-organic framework (MOF)-quorum sensing inhibitor (QSI) antifouling coating on 304 stainless steel (SS) substrates. Inspired by mussel adhesion, a hydrophilic bionic hydrogel was first constructed via metal ion coordination. The traditional metal ion source was replaced with a zeolitic imidazolate framework-8 (ZIF-8) loaded with 2-(5H)-furanone (HF, a QSI) without altering coating formation. Physicochemical characterization using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), the Brunauer–Emmett–Teller (BET) method, and the diffraction of x-rays (XRD) confirmed successful HF loading into ZIF-8 with intact crystal structures. Antifouling tests showed HF@ZIF-8 enhanced antibacterial inhibition against Staphylococcus aureus (97.28%) and Escherichia coli (>97%) and suppressed Chromobacterium violaceum CV026 pigment synthesis at 0.25 mg/mL (sub-growth concentration). The reconstructed PG/PVP/PEI/HF@ZIF-8 coating achieved 72.47% corrosion inhibition via synergistic anodic protection and physical shielding. This work provides a novel green approach for surface antifouling and drag reduction, highlighting MOF-loaded QSIs as promising additives to enhance the antifouling performance of hydrogel coatings, anti-corrosion performance, and QSI performance for sustainable marine engineering applications. 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

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm-forming ability underscore the limitations of current antibiotics. In this study, a new compound named tripterhyponoid A was found to effectively combat MRSA, with an MIC of 2.0 μg/mL. It inhibited biofilm formation by downregulating genes related to the quorum sensing (QS) pathway (sarA, agrA, agrB, agrC, agrD, and hld) and eradicated mature biofilms. Furthermore, it induced DNA damage by binding to bacterial DNA, enhancing its efficiency against MRSA. Therefore, its anti-MRSA properties with multiple mechanisms of action make it less prone to developing resistance over 20 days. In addition, it reduced the bacterial load and regulated the levels of inflammatory cytokines IL-6 and IL-10 at the wound site in a mouse skin infection model. This paper provides the first in-depth investigation of the mechanisms of triterpenoids against MRSA by inhibiting the expression of QS system genes and binding to DNA. 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

Streptococcus agalactiae (GBS) is a major pathogen causing mastitis in dairy cows while causing oxidative stress. Matrine is an alkaloid compound extracted from the roots of Sophora flavescens, a plant used in traditional Chinese medicine. It possesses antioxidant, immunomodulatory, anti-inflammatory, and pro-apoptotic properties. The aim of this study was to investigate the regulatory effects of matrine on the virulence of the ATCC strain (ATCC13813) and clinical GBS strains by transcriptome analysis and qRT-PCR validation. The results showed that the ABC transporter, peptidoglycan biosynthesis, and quorum-sensing pathways were significantly altered in ATCC (4 mg/mL) and GBS (12 mg/mL) strains after matrine treatment at MIC concentrations. Additionally, genes related to invasion and immune escape, including CylE, CAMP, ScpB, and CpsA, and genes related to the expression of adhesion and virulence factors, such as Bac, Lmb, PI2a, and PI2b, were significantly downregulated (p < 0.05). Overall, these data suggest that matrine effectively inhibits the virulence genes of GBS, thereby reducing immune evasion and infection by decreasing the synthesis of capsular polysaccharides and host cell adhesion. Full article

Infections often occur in complex niches consisting of multiple bacteria. Despite the increasing awareness, there is a fundamental gap in understanding which interactions govern microbial community composition. Pseudomonas aeruginosa is frequently isolated from monomicrobial and polymicrobial human infections. This pathogen forms polymicrobial infections with other ESKAPEE pathogens and defies eradication by conventional therapies. By analyzing the competition within co-cultures of P. aeruginosa and representative secondary pathogens that commonly co-infect patients, we demonstrate the antagonism of P. aeruginosa against other ESKAPEE pathogens and the contribution of this pathogen’s multiple quorum-sensing (QS) systems in these interactions. QS is a highly conserved bacterial cell-to-cell communication mechanism that coordinates collective gene expressions at the population level, and it is also involved in P. aeruginosa virulence. Using a collection of P. aeruginosa QS mutants of the three major systems, LasR/LasI, MvfR/PqsABCDE, and RhlR/RhlI, and mutants of several QS-regulated functions, we reveal that MvfR and, to a lesser extent, LasR and RhlR, control competition between P. aeruginosa and other microbes, possibly through their positive impact on pyoverdine, pyochelin, and phenazine genes. We show that MvfR inhibition alters competitive interspecies interactions and preserves the coexistence of P. aeruginosa with the ESKAPEE pathogens tested while disarming the pathogens’ ability to form biofilm and adhere to lung epithelial cells. Our results highlight the role of MvfR inhibition in modulating microbial competitive interactions across multiple species, while simultaneously attenuating virulence traits. These findings reveal the complexity and importance of QS in interspecies interactions and underscore the impact of the anti-virulence approach in microbial ecology and its importance for treating polymicrobial 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

Background/Objectives: This study investigates the phytochemical profile, essential oil composition, and bioactivities—including antioxidant, antimicrobial, antibio-film, and anti-quorum sensing (QS) activities—of four Heracleum L. species (H. crenatifolium Boiss, H. paphlagonicum Czeczott, H. sphondylium subsp. montanum Schleich. ex Gaudin, and H. pastinacifolium subsp. incanum (Boiss. & A.Huet) P.H.Davis). Methods: Total phenolic and flavonoid contents were quantified using the Folin–Ciocalteu and aluminum chloride colorimetric methods, respectively. Essential oils were extracted by hydrodistillation and analyzed via Gas Chromatography–Flame Ionization Detector (GC–FID) and Gas Chromatography–Mass Spectrometry (GC–MS), while Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) evaluated chemical variability among the species. Antioxidant activities were assessed using DPPH and ABTS free radical scavenging assays. Antimicrobial activity was assessed using the broth microdilution method to determine Minimum Inhibitory Concentration (MIC) values, while antibiofilm activity was evaluated using an in vitro microplate-based biofilm model against Pseudomonas aeruginosa PAO1. Anti-QS activity was analyzed using a disc diffusion assay with Chromobacterium violaceum ATCC 12472 as the reporter strain. Results: It was observed that the amounts of total phenolic compounds and total flavonoids were higher in root extracts than in aerial parts extracts for the four species in this study (H. sphondylium subsp. montanum excluding phenolic content). In the analysis of essential oil, it was determined that the major component in the roots was mostly myristicin, and in the fruits it was mostly octyl acetate. Phenolic and flavonoid contents were positively correlated with antioxidant activity. Methanol and n-hexane extracts of H. pastinacifolium (aerial parts) and n-hexane extracts of H. paphlagonicum (root) exhibited notable antimicrobial activity, primarily against Gram-positive bacteria, but none of the extracts showed activity against Klebsiella pneumoniae ATCC 13383 or P. aeruginosa ATCC 27853. Among methanol extracts, H. pastinacifolium (aerial parts) exhibited the highest antibiofilm activity (73.2%), while H. paphlagonicum (aerial parts) showed the highest activity among n-hexane extracts (75.5%). All n-hexane extracts exhibited anti-QS activity, whereas the methanol extracts showed no activity. Conclusions: These findings underscore the chemical diversity and bioactive potential of Heracleum species, contributing to the chemotaxonomic understanding of the genus and supporting their potential applications in medicine and industry. To our knowledge, this is the first study that reveals the antibiofilm and anti-QS properties of these Heracleum species. Full article

Staphylococcus aureus is a formidable pathogen notorious for its antibiotic resistance and diverse virulence mechanisms, including toxin production, biofilm formation, and immune evasion. This article explores innovative anti-virulence strategies to disarm S. aureus by targeting critical virulence factors without exerting bactericidal pressure. Key approaches include inhibiting adhesion and biofilm formation, neutralizing toxins, disrupting quorum sensing (e.g., Agr system inhibitors), and blocking iron acquisition pathways. Additionally, interventions targeting two-component regulatory systems are highlighted. While promising, challenges such as strain variability, biofilm resilience, pharmacokinetic limitations, and resistance evolution underscore the need for combination therapies and advanced formulations. Integrating anti-virulence strategies with traditional antibiotics and host-directed therapies offers a sustainable solution to combat multidrug-resistant S. aureus, particularly methicillin-resistant strains (MRSA), and mitigate the global public health crisis. 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

Microorganisms play a significant role in biofouling and biocorrosion within the maritime industry. Addressing these challenges requires an innovative and integrated approach utilizing marine natural products with beneficial properties. A comprehensive screening of 173 non-toxic EtOAc and H₂O extracts derived from diverse marine organisms collected in Indonesian waters was conducted using a robust panel of assays. These included antimicrobial tests and classical biosurfactant assays (drop collapse and oil displacement), as well as anti-quorum-sensing (QS) and anti-biofilm assays. These screening efforts identified five active extracts with promising activities. Among these, EtOAc extracts of the marine tunicate Sigilina cf. signifera (0159-22e) and the marine sponge Lamellodysidea herbacea (0194-24c) demonstrated significant anti-biofouling activity against Perna indica and anti-biocorrosion performance (mpy 10.70 ± 0.70 for S. cf. signifera; 7.87 ± 0.86 for L. herbacea; 13.60 ± 1.70 for positive control Tetracorr CI-2915). Further chemical analyses of the active extracts, including LC-HR-MS/MS, MS-based molecular networking, and chemoinformatics, revealed the presence of both known and new bioactive compounds. These included tambjamines and polybrominated diphenyl ethers (PBDEs), which are likely contributors to the observed bioactivities. Subsequent investigations uncovered new anti-QS and anti-biofilm properties in synthetic and natural PBDEs 1–12 previously derived from L. herbacea. Among these, 8 exhibited the most potent anti-QS activity, with an IC₅₀ value of 15 µM, while 4 significantly reduced biofilm formation at a concentration of 1 µM. This study highlights the potential of marine-derived compounds in addressing biofouling and biocorrosion challenges in a sustainable and effective manner. Full article