Search Results (107)

The European chestnut (Castanea sativa Mill.) industry generates substantial amounts of underutilized biomass, including shells, leaves, and spiny burs. Distinguishing itself from existing literature, this review presents a novel, integrated life-science analysis that redefines these by-products as a complementary ‘bioactive triad’, ranging from metabolic regulators to anti-virulence agents, rather than interchangeable sources of polyphenols. Although traditionally discarded, these by-products are rich sources of polyphenols, ellagitannins, and flavonoids, with promising potential for nutraceutical, cosmetic, and pharmaceutical applications. This review examines recent advances in the valorization of chestnut by-products, focusing on extraction strategies, chemical profiles, and biological activities. Shell valorization has increasingly shifted toward green extraction technologies, such as subcritical water extraction and deep eutectic solvents, which strongly influence bioactive recovery and composition. Chestnut leaves emerge as a sustainable resource enriched in hydrolysable tannins with anti-inflammatory and quorum sensing-inhibitory properties, particularly relevant for dermatological applications. Spiny burs, often the most phenolic-rich fraction, display marked antioxidant activity and the ability to potentiate conventional antibiotics against pathogens such as Helicobacter pylori. Despite these promising features, major challenges remain, including cultivar-dependent chemical variability, the predominance of in vitro evidence, and safety concerns related to the accumulation of potentially toxic elements. Overall, while chestnut by-products represent valuable resources within circular bioeconomy frameworks, their successful industrial and practical translation will require standardized extraction protocols, robust bioavailability assessments, and well-designed in vivo and clinical studies to ensure safety and efficacy. Full article

Microbial biofilms pose significant medical and industrial challenges due to their resistance to conventional antimicrobials, accounting for 40–80% of bacteria in various environments. This resistance primarily results from the extracellular polymeric matrix, a protective network of sugars, proteins, and other molecules produced by bacteria. The matrix restricts antibiotic penetration, facilitates microbial communication, and retains nutrients. Consequently, novel strategies to counteract biofilms are under investigation. Fatty acids have emerged as promising prebiotic agents, defined as substances that stimulate the growth of beneficial bacteria. These compounds can disrupt biofilm structure and increase microbial susceptibility to treatment. Short- and medium-chain fatty acids demonstrate direct antimicrobial activity and can alter microbial community composition, thereby inhibiting biofilm formation in several pathogens, including oral species. For instance, omega-3 fatty acids effectively inhibit Staphylococcus aureus and Pseudomonas aeruginosa biofilms through membrane disruption and quorum sensing (QS) inhibition. Additionally, long-chain fatty acids, particularly omega-3 and omega-6 polyunsaturated fatty acids, exhibit anti-inflammatory and antibacterial properties. This review synthesises current evidence on fatty acids as prebiotics, emphasising their mechanisms of action and therapeutic potential against drug-resistant biofilm-associated infections. Given the increasing prevalence of antimicrobial resistance, unsaturated and essential fatty acids rep-resent promising candidates for innovative biofilm-control strategies. Full article

Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs) and a major contributor to the global antimicrobial resistance crisis. The increasing prevalence of multidrug-resistant (MDR) strains, including expanded-spectrum β-lactamases (ESBL) and carbapenemase-producing isolates, severely limits treatment options. This review provides an overview on the key molecular mechanisms of UPEC antibiotic resistance, such as enzymatic inactivation, target-site mutations, efflux pump activity, and biofilm formation. Beyond conventional antibiotics, special emphasis is placed on phytochemical strategies as promising alternatives. Flavonoids, alkaloids, terpenoids, and essential oils exhibit antibacterial, anti-adhesive, and antibiofilm properties. These natural bioactive compounds modulate motility, suppress fimbrial expression, inhibit quorum sensing, and enhance antibiotic efficacy, acting both as standalone agents and as adjuvants. Current in vitro and in vivo studies highlight the potential of plant-derived compounds and biologically based therapies to combat UPEC. However, challenges related to standardization, bioavailability, and clinical validation remain unresolved. Integrating molecular mechanistic insights with advanced phytochemical research may offers a sustainable and effective strategy for mitigating UPEC antibiotic resistance. Full article

Background/Objectives: Staphylococcus aureus is a well-known opportunistic pathogen that causes a wide range of infections, from cutaneous blemishes to potentially fatal systemic diseases. The increasing prevalence of antibiotic-resistant bacteria highlights the critical need for alternative therapeutic methods that target virulence factors rather than growth. Methods: The antibacterial activity of 3-fluorocatechol (3-FC) against bacterial and fungal pathogens (e.g., Candida albicans) was determined by broth microdilution to establish the lowest inhibitory concentration. The antibiofilm impact of 3-FC against S. aureus was evaluated using crystal violet staining and viable colony counts, followed by scanning electron microscopy to visualize the biofilm architecture. The methanol extraction method was used to quantify staphyloxanthin synthesis in S. aureus cells. Furthermore, in silico molecular docking was used to evaluate 3-FC binding interactions and provide mechanistic insight into its impacts on S. aureus biofilms and virulence-associated factors. Results: Although the study showed that 3-FC exhibits weak antibacterial activity against S. aureus (MIC > 2048 µg/mL), it shows effective inhibition of up to 86.5% at sub-inhibitory doses during the initial stage of biofilm formation. The CFU enumeration also confirms the significant reduction of viable cell count of S. aureus in the presence of sub-MIC of 3-FC. The SEM analysis confirms disruption of the S. aureus biofilm architecture in the presence of a sub-MIC of 3-FC. Furthermore, the eradication of mature S. aureus biofilm at a sub-MIC dose of 3-FC was 60.6%. 3-FC significantly reduced staphyloxanthin formation, a vital antioxidant pigment that contributes to bacterial pathogenicity, with a maximal suppression of 66.3% at 2048 µg/mL. Molecular docking analyses provide further insight into the molecular basis of 3-FC activity, revealing strong binding affinities with numerous S. aureus virulence regulators and enzymes, suggesting interference with quorum-sensing, adhesion, and oxidative-stress response pathways. Conclusions: Collectively, our findings indicate that 3-FC has antibiofilm and antivirulence properties against S. aureus. Furthermore, this study suggests 3-FC as a viable structural scaffold for the development of a novel anti-infective agent to treat chronic staphylococcal infections. Full article

Antimicrobial resistance (AMR) poses a global health threat, which is becoming more challenging due to the involvement of bacterial virulence mechanisms such as quorum sensing (QS) and biofilm formation. These systems regulate pathogenic traits and shield bacteria from conventional therapies. Phytocompounds offer promising antivirulence strategies by disrupting QS and biofilms without exerting selective pressure. In this study, emodin, a natural anthraquinone, was evaluated for its anti-QS and antibiofilm efficacy. Emodin inhibited violacein production by 63.86% in C. violaceum 12472. In P. aeruginosa PAO1, it suppressed pyocyanin (68.04%), pyoverdin (48.79%), exoprotease (58.55%), elastase (43.13%), alginate (74.12%), and rhamnolipids (56.37%). In S. marcescens MTCC 97, emodin reduced prodigiosin (55.94%), exoprotease (48.80%), motility (83.27%), and cell surface hydrophilicity (41.20%). Biofilm formation was inhibited by over 50% in all three bacteria, highlighting emodin’s potential as a broad-spectrum antibiofilm agent. Molecular docking analyses indicated that emodin exhibited affinity towards QS regulatory proteins CviR, LasR, and SmaR, implying a possible competitive interaction at their ligand-binding sites. Subsequent molecular dynamics simulations confirmed these observations by demonstrating structural stability in emodin-bound proteins. The collective insights from in vitro assays and computational studies underscore the potential of emodin in interfering with QS-mediated virulence expression and biofilm development. Such findings support the exploration of non-antibiotic QS inhibitors as therapeutic alternatives for managing bacterial infections and reducing dependence on traditional antimicrobial agents. Full article

Biofilms are structured microbial communities that adhere to biotic and abiotic surfaces embedded in an autonomous extracellular matrix. These structures contribute to persistent infections, especially in patients with indwelling medical devices, due to their resistance to antimicrobial agents; they have evolved to evade host immune responses. Despite advances in antimicrobial therapies, biofilm-associated infections remain a major challenge in clinical infectious diseases. This perspective explores the underlying mechanisms of biofilm resilience and immune evasion, emphasizing the limitations of conventional treatments and the need to develop pre-emptive measures that focus on preventing biofilm formation rather than implementing a treatment. This work discusses emerging strategies, such as quorum-sensing inhibition, hormonal modulation, matrix-degrading enzymes, anti-adhesive surface modifications, and nanotechnology-based drug delivery, that offer promising avenues to disrupt biofilm formation and maturation. Also offers a shift from the paradigm, looking into proactive prevention rather than treatment, emphasizing clinical translation, scalability, and biocompatibility. Embedding these strategies into routine care could significantly reduce healthcare-associated infections, improve patient outcomes, and mitigate the development of antimicrobial resistance. Our analysis highlights biofilm prevention as a critical frontier in the future of infectious disease management. Full article

This study aimed to evaluate the antibacterial activity of Cistus salviifolius L. and Helichrysum stoechas (L.) DC extracts against S. aureus, including methicillin-resistant S. aureus (MRSA) strains. To this end, assays were conducted to assess killing kinetics, antibiotic combination effects, modulatory effects on ethidium bromide, inhibition of quorum sensing, and biofilm formation. H. stoechas extract demonstrated the strongest activity, with MIC values ranging from 7.8 to 62.5 µg/mL. When combined with antibiotics such as ampicillin, ciprofloxacin, or vancomycin, the extracts of C. salviifolius and H. stoechas predominantly exhibited synergistic (FICI value ≤ 0.5) or additive effects (0.5 < FICI ≤ 1), with some combinations resensitizing resistant strains. The aerial parts of C. salviifolius displayed modulatory effects on ethidium bromide MIC, reducing the concentration from 32 to 8 µg/mL, suggesting efflux pump inhibitory activity. In addition, this extract displayed slight quorum-sensing inhibition at a concentration of 125 µg/mL. Moreover, C. salviifolius and H. stoechas extracts inhibit the formation of biofilm by S. aureus strains, even at subinhibitory concentrations (0.5× and 0.25× MIC). The presence of compounds such as myricetin 3 O-galactoside, catechin derivatives, gallic acid, kaempferol, and chlorogenic acid in the extracts may contribute to their anti-Staphylococcus activity. These results demonstrated the dual antimicrobial and antivirulence potential of C. salviifolius and H. stoechas extracts, highlighting their promise as therapeutic agents or adjuvants against S. aureus. These extracts can be promising candidates for further studies on the development of novel strategies targeting multiple pathogenic pathways. Full article

Background/Objectives: The growing threat of antimicrobial resistance has intensified the search for alternative therapeutic approaches. Quorum sensing (QS) inhibition, which disrupts bacterial communication and virulence, represents a promising approach to mitigating infection. Given the complexity of the sponge holobiont, sponge-associated microorganisms may demonstrate QS inhibitory properties and serve as potential sources of novel anti-virulence agents. This study aimed to investigate the QS inhibitory potential of sponge-associated Bacillus species against Pseudomonas aeruginosa, a multidrug-resistant pathogen that relies on QS for virulence regulation. Methods: Ninety-eight bacterial isolates were obtained from seven intertidal South African sponges. Biosensor-based sandwich assays using Chromobacterium violaceum identified 15 isolates with putative QS inhibition (QSI) activity, including five classified as Bacillus species via 16S rRNA gene sequencing. Crude extracts from these isolates, cultivated in medium Mannitol (Mann) and medium 5294, were screened for their ability to inhibit QS-regulated virulence factors in P. aeruginosa. Results: Extracts, particularly from medium 5294, exhibited significant QSI activity without cytotoxic effects. The five most potent extracts, i.e., Bacillus mobilis SP2-AB7 (5294), Bacillus wiedmannii SP5-AB7 (Mann), B. mobilis SP2-AB7 (Mann), and Bacillus cereus SP1-AB4 (Mann and 5294), inhibited both Las- and Rhl-regulated virulence factors, including pyocyanin, pyoverdine, elastase, protease, rhamnolipid production, motility, and initial adhesion, achieving inhibition rates of up to 93% (p < 0.05). Molecular analysis confirmed the presence of the aiiA lactonase gene in key isolates, while GC-MS and FTIR profiling revealed medium-specific differences in metabolite production. Conclusions: Sponge-associated Bacillus species from KwaZulu-Natal exhibit robust QSI activity against P. aeruginosa, highlighting their potential as sources of alternative anti-virulence agents. Further characterization and in vivo validation are needed to assess their therapeutic application in combatting resistant infections. Full article

The escalating global threat of antimicrobial resistance (AMR) necessitates innovative therapeutic strategies beyond traditional antibiotic development. Drug repurposing offers a rapid, cost-effective approach by identifying new antibacterial applications for existing non-antibiotic drugs with established safety profiles. Emerging evidence indicates that diverse classes of non-antibiotic drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), statins, antipsychotics, calcium channel blockers and antidepressants, exhibit intrinsic antibacterial activity, or potentiate antibiotic efficacy. This review critically explores the mechanisms by which drugs that are not recognised as antibiotics exert antibacterial effects, including efflux pump inhibition, membrane disruption, biofilm inhibition, and quorum sensing interference. We discuss specific examples that demonstrate reductions in minimum inhibitory concentrations (MICs) of antibiotics when combined with these drugs, underscoring their potential as antibiotic adjuvants. Furthermore, we examine pharmacokinetic considerations, toxicity challenges, and clinical feasibility for repurposing these agents as standalone antibacterials or in combination therapies. Finally, we highlight future directions, including the integration of artificial intelligence and machine learning to prioritise drug candidates for repurposing, and the development of targeted delivery systems to enhance bacterial selectivity while minimising host toxicity. By exploring the overlooked potential of non-antibiotic drugs, this review seeks to stimulate translational research aimed at leveraging these agents in combating resistant bacterial infections. Nonetheless, it is crucial to acknowledge that such drugs may also pose unintended risks, including gut microbiota disruption and facilitation of resistance development. Hence, future research should pursue these opportunities with equal emphasis on efficacy, safety, and resistance mitigation. Full article

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

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