Covalent bonding of chitosan to polysulfone, through imine or amine linkages, endows the resulting materials with enhanced hydrophilicity, thermostability, biodegradability and antioxidant and bacteriostatic activity.

Arginine N-Glycosylation of Melittin Enhanced its Bacteriostatic Activity and Antiproliferative Therapeutic Index

Melittin is a natural antimicrobial peptide isolated from bee venom, and the non-specific cytotoxicity and hemolytic activity severely limit its clinical application. Glycosylation of proteins is very common in physiological and biochemical processes and can modulate the interaction of proteins with their target. In this study, eight glycosyl groups were used to modify the arginine of melittin at sites 22 and/or 24, and single and double arginine N-glycosylated peptides were designed and synthesized. Among the acquired 24 glycopeptides, MLT-1c, MLT-3c, MLT-1f, MLT-3f, MLT-1g, and MLT-3h were found to possess higher helicity, while MLT-3c, MLT-3f and MLT-3h showed dramatically reduced hemolytic activity, especially MLT-3c, whose HC50 value is 199.3 μM. MLT-1a, MLT-3a and MLT-2c exhibited improved inhibitory activity against Puzza streptococcus, and the MIC was 4 μg mL-1. MLT-1e and MLT-2g have the strongest tolerance to trypsase, and MLT-3c has the highest therapeutic index. In general, rhamnosyl-modified melittin MLT-3c could be a potent agent for antibacterial and antitumor therapy with high stability and low hemolytic side effects.

ABSTRACT: This study explored antimicrobial alternatives and determined the antibacterial and antibiofilm properties of quercetin against Staphylococcus spp. of goat mastitis. Four bacterial isolates from goats with subclinical mastitis were identified by MALDI-TOF MS: S. aureus, S. chromogenes, S. lugdunensis, S. epidermidis and S. aureus ATCC 25923. We determined the in vitro antibacterial activity of quercetin, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). These concentrations ranged from 1 mg/mL to 0.008 mg/mL. Subsequently, the anti-biofilm activity of quercetin was assessed. The results of this study indicated that quercetin showed bacteriostatic and antibiofilm activity. Subinhibitory concentrations (0.5, 0.25, and 0.125 mg/mL) reduced biofilm. The findings of this study provided a direction for the development of new antimicrobial strategies against Staphylococcus spp. causes of caprine mastitis.

Native and cationic cellulose nanofibril films enriched with avocado seed compounds as a green alternative for potential wound care applications

Antimicrobial resistance (AMR) is problematic for the management of chronic wound infection, where biofilms confer increased tolerance to treatments. A wealth of research describes the antimicrobial activity of essential oils, but none have been formulated for clinical use. We screened ten commercially available essential oils from the Lamiaceae plant family (thyme, rosemary, basil, oregano, clary sage) for bacteriostatic, bactericidal, and anti-biofilm activity. TD-GCMS was used to identify highly abundant compounds which were mapped to efficacy data. Thyme essential oils were antimicrobial against both Pseudomonas aeruginosa and Staphylococcus aureus and had the most potent anti-biofilm activity. Three compounds were common and highly abundant in these oils: o-cymene, 2-isopropyl-4-methyl-phenol (o-thymol/carvacrol), and thymol. The most efficacious red and white thyme oils were formulated into Laponite-based hydrogel emulsions capable of inhibiting both P. aeruginosa and S. aureus in static and dynamic biofilm models. Notably, the efficacy of both gels diverged from that predicted by MIC, MBC, and MBIC values, highlighting the limitations of reductionist analyses in predicting real-world antimicrobial performance.Key points• Thyme oils are the most efficacious of the Lamiaceae plant oils tested• Thymol isomers and o-cymene are abundant in thyme oils, but minor components also play a role in antimicrobial activity• Hydrogel efficacy arises from interactions between formulation and wound microenvironment

Hypercholesterolemia is a major risk factor for cardiovascular diseases. The use of probiotic lactic acid bacteria (LAB) from fermented food products with cholesterol-lowering abilities has emerged as a promising dietary strategy for its management. Lactiplantibacillus plantarum SM14-2STR and Weissella cibaria SE8-2STR were screened and identified by 16S rRNA gene sequencing and were selected for assessment of their probiotic and safety properties, with a focus on their potential antimicrobial activity. Both LAB strains exhibited probiotic potential, sensitivity to multiple antibiotics and ?-hemolytic activity. Moreover, the two selected strains demonstrated remarkable bacteriostatic activity against various pathogenic bacteria (6 out of 9 pathogenic strains) and were capable of surviving under high bile salt concentration (0.3–1%) and low pH conditions (2.0–3.0). L. plantarum SM14-2STR significantly exhibited high cell surface hydrophobicity (~74%) and strong auto-aggregation abilities (~61%). It effectively inhibited the adhesion of Proteus mirabilis DMST 8212 (~60%), whereas W. cibaria SE8-2STR interfered with the growth of Salmonella enterica ATCC 13312 (~61%). Notably, L. plantarum SM14-4STR (84.07±0.89%) and W. cibaria SE8-2STR (39.24±1.19%) significantly showed the highest cholesterol and triglyceride removal capacity in culture media containing 0.3% bile salt (p≤0.05), and both strains exhibited bile salt hydrolase (BSH) activity towards sodium taurocholate. L. plantarum SM14-2STR also significantly inhibited cholesterol uptake in colon epithelial cells by 28.44±0.28%, followed by L. plantarum SM16-4STR at 25.95±0.58% (p≤0.05). These findings indicated that LAB strains derived from fermented meat and Isan sausage may serve as promising probiotics with cholesterol-lowering potential, suitable for applications in the food and health industries.

This study investigated the possibility of imparting bacteriostatic properties to nonwoven polypropylene materials used in the production of medical masks by creating an electret state. The objects of the study were nonwoven polypropylene fabrics manufactured by the Spunbond (density 20 g / m²) and Meltblown (density 25 g / m²) methods, which are most widely used in the medical industry. The antimicrobial effect of the electreted materials was assessed after their treatment with the corona discharge method, and their sensitivity to modified materials was determined by the disk diffusion method on the Mueller-Hinton agar nutrient medium. The study also involved control groups of untreated samples to ensure the reliability of the results. Bacteria most typical of the upper respiratory tract microflora were selected for testing. The results showed that untreated samples did not affect the growth of microorganisms, while electreted fabrics showed selective bacteriostatic activity. It was found that the electret effect suppresses the development of gram-positive bacteria such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus viridians, etc. At the same time, gram-negative microorganisms such as Escherichia coli, Klebsiella pneumoniae, etc. were resistant to the effect. This is explained by differences in the structure of the cell wall: gram-negative bacteria have an additional outer membrane that provides protection from external factors. The data obtained indicate the prospects of using electret polypropylene materials in the production of disposable medical masks. Such products can reduce the risk of spreading airborne infections by suppressing the growth of pathogenic gram-positive bacteria.

This article summarizes the biological activity of 2-bromo-6-(para-tolyl)imidazo[2,1-b][1,3,4]-thiadiazole derivatives in silico conditions using molecular docking. The results of thepredictedbioactive properties of the obtained compounds showed that most of the hybrid compoundsexhibitedhigh antibacterial activity against Mycobacterium tuberculosis. A study of the interactions of derivatives of this heterocycle with amino acids of thetargetprotein cyclopropanase CmaA1 of Mycobacterium tuberculosis showed that someofthesecompounds interacted with a large number of these amino acids through van der Waals, hydrogen,carbon-hydrogen, donor-acceptor, sigma, sulfide-amide, and other bonds: withtyrosine(72),glutamine (69), and glycine (134) via sigma bonds; with amino acids such as valine (9), leucine(90),tryptophan (120), glutamic acid (134), alanine (139), phenylalanine (141), etc., via the electronsofimidazothiadiazole, the tolyl group, the phenyl ring, and the sulfur atom. The obtaineddockingresultsindicate the antituberculosis properties of 2-bromo-6-(p-tolyl)imidazo[2,1-b][1,3,4]-thiadiazolederivatives. Keywords: 6-p-tolyl imidazo[2,1.b][1,3,4]thiadiazole, biological substances, antituberculosis,antimicrobial bacteriostatic activity, bactericidal efficacy, heterobivalent ligand.

The rising threat of multidrug-resistant bacteria necessitates the discovery of novel antibacterial agents with distinctmechanisms of action. In this study, we investigated the antibacterial activity and mechanism of action of Avarol Quinone Terpenoid (AQT), a polyfunctional compound isolated from the marine sponge Neopetrosia exigua, against Staphylococcus aureusATCC 25923. Minimum inhibitory concentration (MIC) testing revealed that AQT exhibits bacteriostatic activity at 2.6 μg/mL and bactericidal activity at 5.2 μg/mL. To further explore its antibacterial mechanism, a series of in vitro assays were performed to assess its impact on bacterial viability, morphology, membrane integrity, and cellular metabolism. Time-kill analysis demonstrated a concentration-dependent reduction in S. aureusviability. Scanning electron microscopy (SEM) revealed severe morphological alterations in AQT-treated cells, including membrane deformation and collapse. Membrane permeability was significantly increased, as indicated by elevated uptake of crystal violet and propidium iodide dyes. These effects were accompanied by marked leakage of nucleic acids, proteins, potassium, calcium, and ATP, supporting membrane disruption. SDS-PAGE analysis showed reduced total protein content, although lipase activity remained unaffected, suggesting AQT does not inhibit protein synthesis. API Staph tests indicated that AQT inhibited sugar utilization (lactose, maltose, and N-acetylglucosamine) and suppressed arginine dihydrolase activity, potentially impairing ATP generation. Autolysis assays showed increased activity of cell wall-degrading enzymes, consistent with cell wall-targeting antibiotics. Furthermore, membrane depolarization assays using DiSC₃(5) confirmed the dissipation of membrane potential. Collectively, these findings suggest that AQT exerts its antibacterial effects through a multifaceted mechanism targeting both the cell wall and the cytoplasmic membrane, leading to loss of membrane integrity, energy depletion, and bacterial cell death. AQT thus holds promise as a potential anti-S. aureustherapeutic agent.

In this study, we evaluated the in vitro antimicrobial activity of ethanolic extracts from the fruits of Daucus carota subsp. carota (wild carrot) and Daucus carota subsp. sativus (cultivated carrot) against five clinically significant bacterial strains: Acinetobacter sp. 12/19, Escherichia coli 83, Streptococcus pneumoniae UEV, Staphylococcus aureus MP1989, and Enterococcus faecalis 26. The antimicrobial activity was determined using the serial dilution method, followed by the establishment of the minimum inhibitory concentration (MIC₅₀) that caused 50% inhibition of the growth of the tested cultures. The results demonstrated a pronounced antimicrobial activity of the tested extracts against all tested strains. The ethanolic extract from D. carota subsp. carota fruits showed higher antimicrobial activity compared to the extract from D. carota subsp. sativus. Specifically, against Acinetobacter sp. 12/19, the extract from wild carrot fruits exhibited a bacteriostatic effect at concentrations starting from 2.0 µg/mL. Against E. coli 83, both extracts demonstrated comparable antibacterial activity, with an MIC₅₀ at the level of 2.0 µg/mL (growth inhibition was 59% relative to the control). However, the minimal bactericidal concentration (MBC) for both extracts was determined as 135 µg/mL, indicating a less pronounced bactericidal effect compared to ceftriaxone, which was used as a reference drug. Against S. pneumoniae UEV, both extracts showed comparable levels of growth suppression across the entire range of tested concentrations, with the percentage of inhibition ranging from 86% (at low concentration) to 93% (at high concentration). Against S. aureus MP1989, both extracts demonstrated bacteriostatic activity in the concentration range of 2.0-135 µg/mL, with a percentage of inhibition from 32.8% to 95.7% for the D. carota subsp. carota extract and from 49.9% to 92.8% for the D. carota subsp. sativus extract. Against E. faecalis 26, the tested extracts were inferior in activity to ceftriaxone, but exhibited a pronounced bacteriostatic effect, with a percentage of inhibition from 69.0% to 96% in the concentration range of 8.0-67.0 µg/mL. The obtained results indicate the promise of further study of the phytochemical composition and antimicrobial potential of Daucus carota fruit extracts for the development of new antimicrobial agents.

The effect of bifido- and lactobacilli complex on some indices of non-specific humoral immunity of sturgeon hybrid Acipenser gueldaenstaedti Brandt × A. baeri Brandt has been studied. The level of antimicrobial properties, C-reactive protein, lysozyme and the content of non-specific immune complexes in serum were studied. The study showed a high level of bacteriostatic activity and lysozyme, low content of nonspecific immune complexes in the experimental groups compared to the control, which indicates the immunostimulating effect of bifidobacteria and lactobacilli complex on nonspecific mechanisms of antibacterial defence of fish.

Background: Foodborne infections are a common occurrence in the world specially since the globalization has emerged. E. coli is one of the main pathogens found in these infections. Different studies on different extracts of Ajwa date have pointed out its antibacterial activity, this study uses Ajwa dates as Such instead of extracts and assesses any activity against E. coli. Methods: Ajwa date pulps were separated, washed, dried and 10 grams dates were blended in 100 ml water. This syrup was mixed with nutrient broth to make different concentrations of Ajwa date. E. coli was inoculated on agar plates to find MBC (minimum bactericidal concentration) and MIC (minimum inhibitory concentration) of Ajwa date pulp. Ampicillin 1 mg/ml was taken as standard. Results: Ajwa date exhibited an MBC of 500 mg/ml while MIC was 250 mg/ml. Conclusion: Ajwa date possesses both bacteriostatic and bactericidal activity against E. coli and can be beneficial in treating foodborne infections caused by E. coli.

Bacteriocins represent a class of secondary metabolites consisting of short peptides with potent bacteriostatic activity and are derived from both Gram-positive and Gram-negative bacterial species. Currently, they are under intense scrutiny in the scientific community. Historically, limited research on bacteriocins, coupled with insufficient understanding of their toxicity signatures and mode of action, has hampered the exploration of antimicrobial resistance. However, recent breakthrough discoveries and validations related to the taxonomic, biosynthetic, and mechanistic foundations of bacteriocins have significantly advanced the development of this field, laying a solid foundation for their development in food preservation, medical, and biological applications. In this comprehensive review, the aim is to present the current status of bacteriocin sources, their different classification schemes, and the complex mechanisms that underpin their biological activity. In addition, this review provides promising avenues for the future application of bacteriocins in the food industry, the medical sector, and the biological sciences, highlighting their potential to revolutionize these fields.

Background: The increased resistance of Gram-negative bacteria, particularly those that produce extended beta-lactamase, are limiting the efficacy of antimicrobial drugs in treating infected diabetic foot ulcers. This study evaluates antimicrobial activities of Napoleona imperialis leaf extracts on bacterial isolates of diabetic foot ulcers as a way of developing novel antimicrobials that will be effective in treating infections caused by multi-drug-resistant (MDR) bacterial isolates. Methodology: Fresh leaves of N. imperialis were collected and identified by a plant taxonomist at the Department of Plant Biology and Biotechnology, Nnamdi Azikiwe University, Awka, Nigeria. The leaves were washed and air- dried under shade and pulverized into fine powder using local milling machine. The pulverized plant was extracted using methanol, hexane, ethyl-acetate, and water. The test organisms used were MDR bacteria isolated from fresh clinical samples collected from patients with diabetic ulcer. The samples were processed using conventional cultures, biochemical identification and molecular detection by PCR methods, and antimicrobial susceptibility testing was done by the disc diffusion technique. The phytochemical compositions of the extract were assessed using standard methods. Antibacterial activity of the extracts was performed at a concentration of 400mg/ml of the extracts using agar well diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MIC) of the extracts were determined using serial (doubling) dilution technique. The time-kill assay of the plant extract was also evaluated. Results: The MDR isolates recovered from the diabetic ulcer were Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. The plant extract yield showed that aqueous fraction of the leaf extract gave higher yield of 37.3%, followed by ethyl acetate fraction of the leaf extract at 26.8%, hexane fraction of the leaf extract at 22.3%, and the least was crude methanol leaf extract at 13.4%. The phytochemical analysis showed that the leaf extracts contained phenols, flavonoid, tannins, glycosides, alkaloids, saponin, terpenoids and triterpenes. The methanol extract produced highest mean inhibition zone diameter of 19.7±00mm against E. coli, 19.3±1.2mm against P. aeruginosa, 19.3±1.2mm against S. pneumoniae, 18.7±1.2mm against S. aureus and 17.7±1.5mm against K. pneumoniae. The bacteriostatic (MIC) activities of this methanol extract at different concentrations ranged from 3.125 to 25.00mg/ml, and bactericidal (MBC) activities ranged from 6.25 to 50.00mg/ml. The time- kill assay of the crude methanol leaf extract at 1xMIC, 2xMIC and 3x MIC showed a decrease in the number of viable cells count of the initial inoculum within 2-8 hours of incubation, indicating high activity. Conclusion: The methanol leaf extracts of N. imperialis could be used as a complementary source of antimicrobials to the conventional antibiotic in the treatment of wound infections caused by MDR bacteria due to the contents of essential secondary metabolites in the plant extract and the antibacterial activities observed.

Fruits are excellent sources of substrate for various fermented products, including fruit vinegars, which are typically produced by submerged fermentation. Some evidence suggests that fruit vinegar consumption can alleviate certain disorders, including hyperlipidemia, inflammation, and hyperglycemia. Fruit vinegars also have bacteriostatic and antihypertensive actions. Recent studies also suggest that apple vinegar may offer benefits in treating insulin resistance, osteoporosis, and certain neurological diseases such as Alzheimer's disease; it may also support weight loss. Recent studies in animal and human models have considerably broadened our understanding of the biological properties of not only fruit vinegars but also oxymels, i.e., mixtures of vinegar and honey or sugar. This paper reviews the current state of knowledge regarding vinegars and oxymels, with a special emphasis on their chemical composition and the mechanisms behind their biological activity and pro-health potential. The multidirectional effects of fruit vinegars and oxymels result from the synergy of different chemical compounds, including organic acids (mainly acetic acid), phenolic compounds, vitamins, minerals, and fermentation products. However, more studies are needed to understand the interactions between all the different components, not only the phenolic compounds and organic acids. In addition, more research is needed on their mechanisms of action. Although no serious side effects have been noted to date, further studies with large sample sizes are needed to understand the possible side effects of long-term fruit vinegar and oxymel use.

Pyrazinamide (PZA) is a critical component of tuberculosis first-line therapy due to its ability to kill both growing and non-replicating drug-tolerant populations of Mycobacterium tuberculosis within the host. Recent evidence indicates that PZA acts through disruption of coenzyme A synthesis under conditions that promote cellular stress. In contrast to its bactericidal action in vivo, PZA shows weak bacteriostatic activity against M. tuberculosis in axenic culture. While the basis for this striking difference between in vivo and in vitro PZA activity has yet to be resolved, recent studies have highlighted an important role for cell-mediated immunity in PZA efficacy. These observations suggest that host-derived antimicrobial activity may contribute to the bactericidal action of PZA within the host environment. In this study we show that the active form of PZA, pyrazinoic acid (POA), synergizes with the bactericidal activity of host-derived reactive oxygen species (ROS). We determined that POA can promote increased cellular oxidative damage and enhanced killing of M. tuberculosis. Further, we find that the thiol oxidant diamide is also able to potentiate PZA activity, implicating thiol oxidation as a key driver of PZA susceptibility. Using a macrophage infection model, we demonstrate the essentiality of interferon-γ induced ROS production for PZA mediated clearance of M. tuberculosis. Based on these observations, we propose that the in vivo sterilizing activity of PZA can be mediated through its synergistic interaction with the host oxidative burst leading to collateral disruption of coenzyme A metabolism. These findings will enable discovery efforts to identify novel host- and microbe-directed approaches to bolster PZA efficacy.

Clostridioides difficile is a major cause of nosocomial infections, often associated with individuals who have gut dysbiosis from previous antibiotic therapies. C. difficile infections (CDI) have a high recurrence rate and impose significant financial and mortality burdens on the healthcare system. Therefore, novel anti-C. difficile drugs are urgently needed to treat and reduce the severity and recurrence of infection. In this study, we screened a library of 618 antiviral drugs to identify a potential candidate for repurposing as novel anti-C. difficile therapeutics. Following our preliminary screening, we identified 9 novel compounds that inhibited C. difficile at a concentration of 16 μM or lower. Among these, 4 antiviral compounds demonstrated the most potent anti-C. difficile activity against a panel of 15 C. difficile isolates, with minimum inhibitory concentrations (MICs) comparable to the drug of choice, vancomycin. These include rottlerin (MIC50 = 0.25 μg/mL), α-mangostin (MIC50 = 1 μg/mL), dryocrassin ABBA (MIC50 = 1 μg/mL), and obefazimod (MIC50 = 4 μg/mL). All exhibited minimal to no activity against representative members of the human gut microbiota. Interestingly, α-mangostin, a natural xanthone derived from the mangosteen fruit, exhibited strong bactericidal action, clearing a high inoculum of C. difficile in less than an hour. All other drugs exhibited bacteriostatic activity. Given their characteristics, these compounds show great promise as novel treatments for CDI.

The widespread resistance of enterococci to many commonly used antimicrobial agents is a growing concern. Given that the current treatment options for enterococcal infections are limited, the discovery of new therapies, including combination therapies, is necessary. We evaluated double-drug combinations of lefamulin with doxycycline, rifampin, and quinupristin/dalfopristin for in vitro synergy against strains of Enterococcus faecium (E. faecium) and Enterococcus faecalis (E. faecalis) by using checkerboard and time-kill assays. In the checkerboard assay, the synergistic effect of lefamulin with doxycycline and rifampin was observed in 29 (85.3%) and 33 (97.1%) of the 34 different E. faecium strains tested, respectively. These combinations also showed synergistic effects against 17 (94.4%) of the 18 different vancomycin-resistant E. faecium strains. Among the 33 different E. faecalis strains, the combination of lefamulin with doxycycline, quinupristin/dalfopristin, and rifampin displayed synergistic effects in 31 (93.9%), 26 (78.8%), and 20 (60.6%) strains, respectively. No antagonism was observed in any of the combinations. The time-kill assay confirmed the synergistic effects of all these combinations. These synergistic combinations exhibited bacteriostatic activity. Although lefamulin is not currently used to treat enterococcal infections, we suggest that these combinations may serve as alternative drug regimens.

This work presents a comprehensive investigation into the design, synthesis, and evaluation of a novel series of 4-alkoxyquinolines as potential antimycobacterial agents. The design approach, which combined molecular simplification and chain extension, resulted in compounds with potent and selective activity against both drug-susceptible and multidrug-resistant Mycobacterium tuberculosis strains. The lead molecule, targeting the cytochrome bc1 complex, exhibited favorable kinetic solubility and remarkable chemical stability under acidic conditions. Despite in vitro ADME evaluations showing low permeability and high metabolism in rat microsomes, the lead compound exhibited bacteriostatic activity in a murine macrophage model of TB infection and demonstrated promising in vivo exposure following gavage in mice, with an AUC0-t of 127.5 ± 5.7 μM h. To the best of our knowledge, for the first time, a simplified structure from 2-(quinolin-4-yloxy)acetamides has shown such potential. These findings suggest a new avenue for exploring this chemical class as a source of antituberculosis drug candidates.