Potent Antibacterial Activity Research Articles

Design, synthesis, and biological evaluation of steroidal indole derivatives as membrane-targeting antibacterial candidates.

Rational modification of natural products plays a key role in drug discovery. Herein, a series of steroidal indole derivatives containing various substituents and steroidal skeletons were designed and synthesized with classical Fischer indole synthesis as a key step in an efficient synthetic route for the first time. The in vitro antibacterial activity of all the synthesized derivatives was evaluated against four Gram-positive strains including three Methicillin-Resistant Staphylococcus aureus. Compound 11e displayed the most potent antibacterial activity (MIC=1-2μg/mL) with low cytotoxicity and hemolytic activity. Derivative 11e displayed more rapid bactericidal kinetic than vancomycin in the time-kill study and was less likely to induce bacterial resistance. Moreover, the preliminary antibacterial mechanism explorations indicated that compound 11e could effectively inhibit biofilm formation, promote the accumulation of reactive oxygen species, decrease bacterial metabolism, and destroy bacterial cell membranes to exert its antibacterial effects. The study of in vivo antibacterial activity suggested that compound 11e could significantly reduce the bacteria counts in a mouse subcutaneous infection model. These findings provided a bright hope for steroidal indole derivatives as promising antibacterial candidates to settle drug resistance.

Biocontrol of virulent Listeria monocytogenes using green carboxylated cellulose nanocrystals-silver nano-biohybrids.

L. monocytogenes is a Gram-positive bacterial pathogen, known to cause food poisoning and systemic disease, specifically listeriosis. This species has shown resistance to many commonly used antibiotics, making the search for new alternative therapies is a pressing matter. A facile and eco-friendly sono-co-method was developed to produce Ag nanoparticles from palm sheath fiber agricultural waste, using carboxylated cellulose nanocrystals (CCNs). Spectroscopic analysis, including UV-visible, TEM, FTIR, and EDS, confirmed the successful synthesis of the CCN-Ag nano-biohybrids. The nano-biohybrids exhibited potent antibacterial activity against various L. monocytogenes strains, with inhibition zones ranging from 16 to 19 mm. Concentrations of the CCN-Ag suspension between 0.25 and 1 μg/mL were found to completely prevent the growth of L. monocytogenes. Conventional PCR analysis revealed the presence of several virulence genes, including actA, inlA, inlB, plcA, iap, and hlyA, in all the tested strains. Notably, CCN-Ag treatment significantly downregulated these genes, indicating a reduction in virulence and potential for biocontrol applications. The novelty of this research lies in the development of a sustainable and eco-friendly method for producing potent antimicrobial nanohybrids from agricultural waste. These nanohybrids' ability to effectively inhibit L. monocytogenes' growth and downregulate its virulence genes offers a promising avenue for combating this pathogenic bacterium.

P-1246. Effect of BV100 on the Pharmacokinetics of Midazolam and its metabolite 1-hydroxymidazolam in healthy volunteers

Abstract Background We identified rifabutin as having potent antibacterial activity towards Acinetobacter baumannii under iron limiting conditions. BV100 (rifabutin for infusion) is under development for the treatment of serious infections due to A. baumannii A single center, open-label, 3-period fixed-sequence, phase I clinical drug-drug interaction study was conducted to evaluate the effect of BV100 on the pharmacokinetics (PK) of midazolam and its metabolite 1-hydroxymidazolam on healthy subjects. Methods The study included nonchildbearing females and males aged 18 to 55. The study was divided in three periods : On Day 1 (Period 1), each participant received a single 5 mg oral dose of midazolam syrup. After a 24-hour washout on Day 2, BV100 was given as a 300 mg intravenous infusion over 2 hours every 12 hours for 8 doses from Day 3 to Day 6 (Period 2). On Day 7 (Period 3), the 9th dose of BV100 was administered alongside a single 5 mg oral dose of midazolam. PK parameters for midazolam and its metabolite were assessed in plasma samples on Day 1 after midazolam administration alone and on Day 7 after midazolam administration following 8 BV100 doses from Day 3 to Day 6. Results No deaths, no SAEs, or other significant AEs occurred during this study. All 23 study subjects were eligible for safety analysis. Sixteen out of 23 subjects completed all 3 periods of the study. No clinically relevant effects of BV100 on clinical laboratory profiles (haematology, biochemistry, haemostasias, urinalysis) or vital signs (blood pressure, heart rate, respiration rate, body temperature) were observed in this study. Midazolam and 1-OH-midazolam plasma concentrations were higher when administered alone on Day 1 (Cmax = 33.36 ng/mL; AUC0-tlast = 99.20 h*ng/mL) compared to co-administration with BV100 on Day 7 (Cmax = 25.43 ng/mL; AUC0-tlast = 50.81 h*ng/mL). The elimination parameters indicate faster elimination for both midazolam and its metabolite on Day 7 compared to Day 1. Conclusion BV100 is considered a mild and weak inducer of midazolam according to EMA and FDA criteria, respectively. Multiple 300 mg IV doses of BV100, administered with and without midazolam to healthy subjects, were safe and well tolerated. Disclosures All Authors: No reported disclosures

Discovery of Metabolic Reprogramming 2-Quinolones as Effective Antimicrobials for MRSA-Infected Wound Therapy.

To date, the abuse of antibiotics and a gradual decline in novel antibiotic discovery enlarge the threat of drug-resistant bacterial infections, especially methicillin-resistant Staphylococcus aureus (MRSA). Herein, inspired by the unique structures and antibacterial activities of 2-quinolones, a class of novel 2-quinolones with substituted pyridines was synthesized. Notably, compound 11, the derivative with a methylpyridine fragment, showed potent antibacterial and antibiofilm activities, especially for MRSA strains (MIC = 0.02-0.04 μg/mL). A mechanistic study of compound 11 revealed that the increase of intracellular ROS and acceleration of the TCA cycle, which reprogrammed the bacterial metabolism, eventually triggered membrane damage and bacterial death. Most importantly, compound 11, with antibacterial and anti-inflammatory properties, accelerated the reconstruction and healing of MRSA-infected cutaneous wounds by decreasing bacterial loads, attenuating inflammation, and promoting angiogenesis. Overall, these findings provide a novel multifunctional chemotype with broad-spectrum antibacterial activity and highlight a promising strategy for MRSA-infected wound healing.

Efficacy Evaluation of Jania rubens Extract Against Four Pathogenic Strains Associated with Foodborne Disease in Iran

This study evaluated the antimicrobial properties of Jania rubens algae extract, obtained via Soxhlet extraction, against food spoilage and pathogenic bacteria. Using response surface methodology and the Box-Behnken design, the research optimized extraction parameters, including solvent type, solvent-to-algae ratio, and extraction duration. Antimicrobial efficacy was assessed through the zone of inhibition (ZOI), Minimum Inhibitory Concentration (MIC), and Minimum Bactericidal Concentration (MBC) against Escherichia coli, Salmonella enteritidis, Staphylococcus aureus, and Bacillus cereus. Results showed MIC and MBC values for E. coli ranged from 0.32–1.5 and 2–3, respectively; for S. enteritidis, 0.98–1.9 and 2.5–3.5; for S. aureus, 0.4–1.5 and 0.8–2.8; and for B. cereus, 0.36–1.35 and 0.85–1.85. Optimal extraction conditions included acetone as the solvent, a 5:1 solvent-to-algae ratio, and extraction durations of 2 or 6 hours. The algae extract significantly extended the lag phase and reduced bacterial growth rates, with effects intensifying at higher concentrations. The study concludes that Jania rubens extract, particularly under optimized Soxhlet extraction conditions, exhibits potent antibacterial activity, making it a promising natural antimicrobial agent for food preservation.

Efficacy Evaluation of Jania rubens Extract Against Four Pathogenic Strains Associated with Foodborne Disease in Iran

This study evaluated the antimicrobial properties of Jania rubens algae extract, obtained via Soxhlet extraction, against food spoilage and pathogenic bacteria. Using response surface methodology and the Box-Behnken design, the research optimized extraction parameters, including solvent type, solvent-to-algae ratio, and extraction duration. Antimicrobial efficacy was assessed through the zone of inhibition (ZOI), Minimum Inhibitory Concentration (MIC), and Minimum Bactericidal Concentration (MBC) against Escherichia coli, Salmonella enteritidis, Staphylococcus aureus, and Bacillus cereus. Results showed MIC and MBC values for E. coli ranged from 0.32–1.5 and 2–3, respectively; for S. enteritidis, 0.98–1.9 and 2.5–3.5; for S. aureus, 0.4–1.5 and 0.8–2.8; and for B. cereus, 0.36–1.35 and 0.85–1.85. Optimal extraction conditions included acetone as the solvent, a 5:1 solvent-to-algae ratio, and extraction durations of 2 or 6 hours. The algae extract significantly extended the lag phase and reduced bacterial growth rates, with effects intensifying at higher concentrations. The study concludes that Jania rubens extract, particularly under optimized Soxhlet extraction conditions, exhibits potent antibacterial activity, making it a promising natural antimicrobial agent for food preservation.

Inhibitors of NADH-O-methylquinone compound a class of antitubercular drugs.

Disruption of the mycobacterial redox homeostasis leads to irreversible stress induction and cell death. Hydroquinone scaffolds, as a new type of redox cycling anti-tuberculosis chemotypes, exhibit potent bactericidal activity against non-replicating, nutrient-deprived phenotypically drug-resistant bacteria. Evidences from microbiological, biochemical, and genetic studies indicate that the redox-driven mode of action relies on the reduction of quinones by type II NADH dehydrogenase (NDH2), generating reactive oxygen species (ROS) of bactericidal level. This study demonstrates that (S)-Peniphenone D possesses significant resistance to Mycobacterium marinum (M. marinum) infection, as it enables redox cycling within M. marinum cells, ROS production, and reduction of intracellular NADH levels. The results suggest that hydroquinone compounds, due to their distinctive biological activities, could serve as novel sources for antibacterial drugs, particularly in developing scaffolds for new anti-tuberculosis agents.

Hexagonal zinc oxide nanoparticles: a novel approach to combat multidrug-resistant Enterococcus faecalis biofilms in feline urinary tract infections

IntroductionEnterococcus faecalis, a common inhabitant of the feline gastrointestinal tract, has emerged as a significant pathogen causing urinary tract infections (UTIs) in domestic cats. The rise of multidrug-resistant E. faecalis strains and their propensity to form biofilms pose significant challenges in treatment. This study investigated the antibacterial and antibiofilm activities of hexagonal zinc oxide nanoparticles (ZnONPs) alone and in combination with streptomycin and Moringa oleifera leaf extract (MOLe) against multidrug-resistant E. faecalis isolates from feline UTIs.MethodsAntimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Biofilm formation was assessed using the crystal violet assay, and biofilm-associated genes (sprE, gelE, fsrABC) were detected by PCR. ZnONPs, Str/ZnONPs (streptomycin-loaded ZnONPs), and Str/MOLe@ZnONPs (streptomycin and MOLe-loaded ZnONPs) were characterized using FTIR, DLS, TEM, and SEM. The antibacterial and antibiofilm activities of the synthesized nanoparticles were evaluated through time-kill assays, well diffusion assays, and gene expression analysis.ResultsA high prevalence of multidrug resistance was observed among the E. faecalis isolates, with significant resistance to ampicillin, vancomycin, and streptomycin. Characterization studies revealed the successful encapsulation of streptomycin and MOLe within the ZnONPs.In vitro assays demonstrated that Str/MOLe@ZnONPs exhibited potent antibacterial and antibiofilm activities against the tested E. faecalis strains, significantly reducing bacterial growth and biofilm formation.DiscussionThe emergence of multidrug-resistant E. faecalis strains necessitates the development of novel therapeutic strategies. This study demonstrates the promising potential of ZnONPs, particularly those loaded with streptomycin and MOLe, in combating biofilm-forming E. faecalis. The synergistic effects of the combined formulation may offer a novel approach to overcome antibiotic resistance and improve the treatment outcomes of E. faecalis UTIs in domestic cats.

Comprehensive safety and toxicity analysis of 2,2’-Bipyridine derivatives in combating MRSA biofilm formation and persistence

IntroductionMethicillin-resistant Staphylococcus aureus (MRSA) infections have become arduous to treat due to their capacity to form biofilms, develop persistence, and exhibit significant antimicrobial resistance. These factors contribute to the complexity of managing MRSA infections and highlight the urgent need for innovative treatment strategies.ObjectivesThis endeavor aims to evaluate the safety of 2,2’-Bipyridine (2,2’-Bipy) derivatives and their antimicrobial, anti-biofilm, and anti-persister activities in treating MRSA Infections.MethodsSix derivatives were screened for their ADMET properties and tested for minimum inhibitory concentrations against various bacterial strains using agar well diffusion and broth dilution. Safety studies were conducted through hemolysis tests, cell viability assays, and in vivo acute oral toxicity examinations. Bactericidal mechanisms and biofilm disruption effects were analyzed using crystal violet staining and confocal microscopy assays. The murine thigh infection model was also used to investigate the in vivo efficacy.ResultsAll derivatives exhibited favorable physicochemical profiles and ADMET properties and are predicted to be safe based on their drug-like properties. in vitro studies demonstrated that derivatives are non-toxic to 3T3 L1, and in vivo studies confirmed their safety in mice at a dose of 300 mg/kg and their non-hemolytic nature against rabbit red blood cells. All compounds showed potent antibacterial activity against the tested bacteria, including the resistant MRSA strain 831. They inhibited biofilm formation and eradicated biofilms in a dose-dependent manner against MTCC 737 and MRSA 831, and they effectively eliminated MRSA persister cells, outperforming the reference antibiotic vancomycin. These derivatives were found to depolarize the mitochondrial membrane and accumulate intracellular reactive oxygen species. These derivatives significantly reduced the bacterial load in the murine thigh infection model.ConclusionThe study concluded that 2,2’-Bipy derivatives possess significant antimicrobial activity, are non-toxic, and are effective in inhibiting biofilm formation and killing persister cells.

Ligand-free palladium-catalyzed synthesis of 3-(2,2-dialkyl-2H-chromen-4-yl)-2-phenylimidazo[1,2-a]pyridine derivatives: molecular docking investigation of their potential as DNA gyrase inhibitors and evaluation of their antibacterial activities.

Palladium-catalyzed reactions between imidazo[1,2-a]pyridine derivatives and 4-bromo-2,2-dialkyl-substituted 2H-chromenes under microwave irradiation at 100 W, 120 °C for 20-30 min provided a series of new 3-(2,2-dialkyl-2H-chromen-4-yl)-2-phenylimidazo[1,2-a]pyridine derivatives in good to excellent yields. The structures of the synthesized compounds were confirmed through spectroscopic techniques (NMR and HRMS). The X-ray single-crystal structure of compound 16e was also determined. Shorter reaction time, high yield and good substrate scope were the major advantages of this method. All these compounds were further investigated in vitro for the evaluation of their antibacterial potency using the agar well diffusion method against human pathogenic Gram-negative E. coli and Gram-positive S. aureus bacteria, with the determination of their minimum inhibitory concentration (MIC) values. Indeed, compound 16h strongly inhibited DNA gyrase in silico with a binding affinity of -8.7 kcal mol-1 and exhibited zone of inhibition (ZI) values of 19 mm and MIC values of 10 μg mL-1 in both Gram-negative E. coli and Gram-positive S. aureus, relative to the standard drug gentamicin. By analyzing the structure-activity relationships based on the molecular docking results and the potent antibacterial activities, it could be concluded that these new phenylimidazo[1,2-a]pyridine-chromene derivatives have the potential to be effective druggable antibacterial agents.

Exploring the Anti-Adherence Potential of Skt35 to Combat Catheter-Associated Staphylococcus aureus Infections: Efficacy, Toxicity and Mechanism of Action.

Catheter-associated urinary tract infections (CAUTIs), often caused by biofilm-forming Staphylococcus aureus, present significant clinical challenges. Skt35, a dioxopiperidinamide derivative of cinnamic acid, was investigated for its potential antibacterial and antibiofilm activities against S. aureus biofilms. The antibacterial effect of Skt35 was assessed using the zone of inhibition and microdilution methods, revealing a minimum inhibitory concentration (MIC) of 250µM. Antibiofilm properties were confirmed through crystal violet assays, scanning electron microscopy and confocal laser scanning microscopy, showing significant biofilm inhibition at the Sub-MIC. In an in vitro bladder model, Skt35-coated silicone catheter tubes exhibited significant antiadhesive effects. Zebrafish embryo tests indicated no toxicity at concentrations up to 125µM. Molecular docking and simulation analysis revealed strong binding affinities of Skt35 to Accessory Gene Regulator A (-7.9kcal/mol) and Lux Small protein (-4.96kcal/mol), suggesting potential disruption of quorum sensing and gene expression in S. aureus, making it a promising candidate for catheter coatings to prevent CAUTIs.

Green synthesis of Ag-Fe bimetallic nanoparticles using fungal filtrates: unlocking multifunctional medical and environmental applications.

The current investigation focuses on synthesizing Ag-Fe bimetallic nanoparticles (AgFe-BMNPs) using cell-free filtrates of the Gymnascella dankaliensis as a novel fungal reducing agent. The optical, morphological, and surface properties of these fungus-fabricated AgFe-BMNPs and their monometallic counterparts (AgNPs and FeNPs) were analyzed using sophisticated nanotechnology instruments. The UV-visible spectrum showed peaks at 231 nm and 415 nm for BMNPs and 450 nm and 386 nm for AgNPs and FeNPs, respectively. XRD diffractograms revealed crystallographic peaks at 32.96°, 35.32°, and 49.32° for AgFe-BMNPs with crystalline size of 10.68 nm. FTIR spectrum indicates peaks at 954 cm-1 (M-O bond) and 599 cm-1 (M-C\M-L bond). Agglomerated, spherical BMNPs with a mean size of 96.76 nm were spotted in SEM micrographs. The BMNPs were tested for anticancer and antibacterial activities, dye removal efficiency, and seed germination enhancement. The anticancer study found that AgFe-BMNPs hold promising potential for application in breast cancer therapy with a 1 μg mL-1 IC50 value. It also exhibited potent antibacterial activity with a 50 μg mL-1 concentration against Bacillus cereus,Serratia marcescens, Bacillus megaterium, and Staphylococcus aureus. A comparative batch adsorption study for methylene blue dye removal over 180 min showed removal capabilities of 89% for BMNPs. Different concentrations (0.02, 0.04, 0.08 mg mL-1) of BMNPs also demonstrated superior efficiency up to 90% enhanced seed germination at the 6 h mark and 91.87% enhanced water retention capacity in Vigna radiata. This research underscores the medical, environmental, and agricultural potential of AgFe-BMNPs, highlighting their multifaceted benefits in nanotechnology.

Bactericidal Hemostatic Sponge: A Point of Care Solution to Combat Traumatic Injury.

Uncontrollable haemorrhage and associated microbial contamination in the battlefield and civilian injuries pose a tremendous threat to healthcare professionals. Such traumatic wounds often necessitate an effective point-of-care solution to prevent the consequent morbidity owing to blood loss or haemorrhage. However, developing superior hemostatic materials with anti-infective properties remains a challenge. To address this, an injectable, cationic dextran-mesoporous silica nanoparticle-based bactericidal hemostatic sponge (BACSTAT) has been developed. A dual crosslinking approach is adopted through in situ covalent cross-linking through photo polymerization and silica nanoparticle-induced non-covalent interactions. This interconnected macroporous BACSTAT sponge has superior fluid absorption properties and fluid-induced rapid shape recovery of the sponge helps to seal the irregularly shaped wound. Furthermore, this sponge can stimulate a coagulation cascade for rapid blood clotting in mice femoral vein incision and liver puncture model. The optimum sponge exhibited potent antibacterial activity against wide-spectrum Gram-positive and Gram-negative pathogens. Notably, it is completely biocompatible with mammalian cells and mice skin. Significantly, this sponge reduces Pseudomonas aeruginosa burden >99% in mice subcutaneous infection model with substantially lessening inflammatory responses in infected tissues. Collectively, the optimized sponge bears immense potential to be developed as point-of-care solution for military and civilian traumatic injury.

Novel tetracycline hybrids: synthesis, characterization, docking studies and in-vitro evaluation of antibacterial activity

BackgroundThe biggest menace in the world today is the infection caused by pathogenic bacteria in humans, where majority of the available antibiotics fail to provide therapeutic results due to resistance. The discovery of new molecules is the need of the hour and several research groups worldwide are contributing to fight this scare. This work highlights our efforts towards discovering novel tetracycline hybrids that could serve as potent agents against several pathogenic bacterial strains causing infections. In total, ten compounds were synthesized which were chemically conjugates of Minocycline, an age-old tetracycline, and naturally occurring aldehydes and ketones available from the plant sources. Structural characterization of these compounds was done using Mass and 1HNMR. Molecular docking was carried out in order to predict the binding affinity of these compounds to various bacterial enzymes and known protein targets and to establish the structure–activity relationships. Molecular dynamic simulation studies and in silico pharmacokinetic and toxicity prediction studies were done to determine in silico pharmacokinetics and toxicity of compounds. In-vitro antibacterial activities were done using standard protocols against gram positive bacteria like Enterococcus faecalis, Staphylococcus aureus and gram-negative bacteria like Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli.ResultsPromising results were obtained viz. compound 1,2 and 10 were found to be more potent against Staphylococcus aureus, compound 1 against Enterococcus faecalis, compound 2 and 3 against Escherichia coli, compound 7 and 8 against Pseudomonas aeruginosa and compound 7 against Klebsiella pneumoniae when compared with minocycline as standard compound.ConclusionAll the synthesized compounds were screened for their anti-bacterial activity against gram positive and gram negative microorganisms. Amongst the ten synthesized minocycline hybrids, four minocycline hybrids exhibited potent antibacterial activity as compared to minocycline. These hybrids can serve as a promising lead compound for antibiotic drug discovery.

Self-Assembled Peptide Hydrogels PPI45 and PPI47: Novel Drug Candidates for Staphylococcus aureus Infection Treatment.

Staphylococcus aureus, a prevalent zoonotic pathogen, poses a significant threat to skin wound infections. This study evaluates the bactericidal efficacy of self-assembled peptide hydrogels, PPI45 and PPI47, derived from the defensin-derived peptide PPI42, against S. aureus ATCC43300. The high-level preparation of PPI45 and PPI47 was achieved with yields of 1.82 g/L and 2.13 g/L, which are 2.19 and 2.60 times the yield of PPI42. Additionally, the critical micelle concentrations (CMCs) of the peptides at pH 7.4 for PPI42, PPI45, and PPI47 were determined to be 245 µg/mL, 973 µg/mL, and 1016 µg/mL, respectively. At a concentration of 3 mg/mL, the viscosities of the gels were 52,500 mPa·s, 33,700 mPa·s, and 3480 mPa·s for PPI42, PPI45, and PPI47. Transmission electron microscopy (TEM) revealed that all peptides exhibited long, pearl necklace-like protofibrils. These peptides demonstrated potent bactericidal activity, with a minimal inhibitory concentration (MIC) of 4-16 µg/mL against S. aureus, and a sustained effect post-drug clearance. Flow cytometry analysis after 2×MIC peptides treatment for 2 h revealed a 20-38% membrane disruption rate in bacteria, corroborated by scanning electron microscopy (SEM) observations of membrane damage and bacterial collapse. The peptide treatment also led to reduced hyperpolarized membrane potential. In vitro safety assessments indicated minimal hemolytic activity on murine red blood cells and low cytotoxicity on human immortalized epidermal cells (HaCaT). In summary, this work lays a valuable cornerstone for the future design and characterization of self-assembling antimicrobial peptides hydrogels to combat S. aureus infection.

Combating Antibiotic-Resistant Bacterial Infection Using Coassembled Dimeric Antimicrobial Peptide-Based Nanofibers.

The emergence of multidrug-resistant (MDR) pathogens, coupled with the limited effectiveness of existing antibiotics in eradicating biofilms, presents a significant threat to global health care. This critical situation underscores the urgent need for the discovery and development of antimicrobial agents. Recently, peptide-derived antimicrobial nanomaterials have shown promise in combating such infections. Amino acid noncovalent forces, notably π-π stacking and electrostatic interactions, remain underutilized for guiding the coassembly of peptides into bacteriostatic nanomaterials. Thus, we constructed a dimeric nanopeptide system using the disulfide bonds of cysteine. The self-assembly of dimeric peptides into nanofibers was realized by the interaction of π-π aromatic amino acids (Trp, Phe, and Pyr) and the electrostatic attraction between oppositely charged amino acids (Asp and Arg). The optimal dimeric peptide 2D2W exhibits potent antibacterial activity against resistant bacteria and is nontoxic. Mechanistically, 2D2W penetrated the outer membrane after electrostatic adsorption, resulting in plasma membrane depolarization, homeostatic disruption, and ultimately bacterial death. In a mouse model of peritonitis, 2D2W demonstrated efficacy in the in vivo treatment of bacterial infections. In conclusion, the design of dimeric nanopeptides co-driven by intermolecular forces provides a promising avenue for the development of high-performance antimicrobial nanomaterials. These advances may also facilitate the application and advancement of peptide-based bacteriostatic agents in clinical practice.

Antibacterial Activity of Selected Essential Oil Components and Their Derivatives: A Review.

Essential oils (EOs) are gaining ground and have been intensively studied due to their widespread use in the pharmaceutical, food, and cosmetics industries. The essential components of EOs have been recognized for diverse therapeutic activities and have gained significant attention for their potential antibacterial activities. Despite the popularity of EOs and potent biological properties, their bioactive components and their derivatives are still not comprehensively characterized. This review explores the antibacterial efficacy of selected EO components and their derivatives, focusing on monoterpenes chosen (i.e., carvacrol, menthol, and thymol) and phenylpropanoids (i.e., cinnamaldehyde and eugenol). Furthermore, this review highlights recent advancements in developing derivatives of these EO components, which have shown improved antibacterial activity with reduced toxicity. By summarizing recent studies, this review reveals the potential of these natural compounds and their derivatives as promising candidates for pharmaceuticals, food preservation, and as alternatives to synthetic antibiotics in combating bacterial resistance.

Novel Leech Antimicrobial Peptides, Hirunipins: Real-Time 3D Monitoring of Antimicrobial and Antibiofilm Mechanisms Using Optical Diffraction Tomography.

Antimicrobial peptides (AMPs) are promising agents for treating antibiotic-resistant bacterial infections. Although discovering novel AMPs is crucial for combating multidrug-resistant bacteria and biofilm-related infections, their clinical potential relies on precise, real-time evaluation of efficacy, toxicity, and mechanisms. Optical diffraction tomography (ODT), a label-free imaging technology, enables real-time visualization of bacterial morphological changes, membrane damage, and biofilm formation over time. Here, a computational analysis of the leech transcriptome using an advanced AI-based peptide screening strategy with ODT to identify potential AMPs is employed. Among the 19 potential AMPs identified, hirunipin 2 demonstrates potent antibacterial activity, low mammalian cytotoxicity, and minimal hemolytic effects. It demonstrates efficacy comparable to melittin, resistance to physiological salts and human serum, and a low likelihood of inducing bacterial resistance. Microscopy and 3D-ODT confirm its disruption of bacterial membranes and intracellular aggregation, leading to cell death. Notably, hirunipin 2 effectively inhibits biofilm formation, eradicates preformed biofilms, and synergizes with antibiotics against multidrug-resistant Acinetobacter baumannii (MDRAB) by enhancing membrane permeability. Additionally, hirunipin 2 significantly suppresses pro-inflammatory cytokine expression in LPS-stimulated macrophages, highlighting its anti-inflammatory properties. These findings highlight hirunipin 2 as a strong candidate for developing novel antibacterial, anti-inflammatory, and antibiofilm therapies, particularly against multidrug-resistant bacterial infections.

3D printed Aloe barbadensis loaded alginate-gelatin hydrogel for wound healing and scar reduction: In vitro and in vivo study.

Wounds are one of the most critical clinical issues in plastic surgery repair and restoration. Conventional wound dressing materials cannot absorb enough wound exudates and shield the site from microbial infection. Also, despite their healing prowess, bioactive molecules from medicinal plants are less bioavailable at the wound sites. This study developed a 3D-printed hydrogel of sodium alginate and gelatin loaded with freeze-dried Aloe barbadensis extract for enhanced wound healing. The hydrogel was hydrophilic and showed an average pore size of 163.66 ± 14.45 μm, moderate swellability, and ideal mechanical properties with tensile strength(σ) of 16.39 ± 0.98 MPa, and Young's modulus of 17.43 ± 1.41 MPa. They showed potential antibacterial activity against Staphylococcus aureus (87.7 ± 4 % inhibition) and Pseudomonas aeruginosa (84.4 ± 6 % inhibition). These hydrogels were hemocompatible, biocompatible, and biodegradable. Cell cytotoxicity assay and scratch assay showed effective Normal Human Dermal Fibroblast cells (NHDF) viability, proliferation, and migration on the hydrogel. In vivo studies of the 3D-printed hydrogel demonstrated significantly improved wound closure, reduced wound contraction, enhanced epithelial regeneration with minimal inflammation, and decreased scar formation after 14 days of treatment. Therefore, this 3D-printed hydrogel can be promising for wound healing with scar reduction.

Study of an arginine- and tryptophan-rich antimicrobial peptide in peri-implantitis.

The combination of hydrophilic arginine residues and hydrophobic tryptophan residues is considered to be the first choice for designing short-chain antimicrobial peptides (AMPs) due to their potent antibacterial activity. Based on this, we designed an arginine- and tryptophan-rich short peptide, VR-12. Peri-implantitis is a significant microbial inflammatory disorder characterized by the inflammation of the soft tissues surrounding an implant, which ultimately leads to the progressive resorption of the alveolar bone. This study found through antibacterial experiments, wound healing promotion experiments, and anti-inflammatory experiments that VR-12 inhibited and killed planktonic peri-implantitis-associated bacteria, inhibited biofilm formation, and disrupted mature biofilms. Additionally, VR-12 exhibited good biocompatibility with RAW264.7 cells and human gingival fibroblasts (HGFs) cells, promoting proliferation of both cell types. Moreover, VR-12 induced HGFs migration by promoting expression of migration-related factors, thereby promoting soft tissue healing. VR-12 also acted on lipopolysaccharide (LPS)-induced RAW264.7 cells, exerting excellent anti-inflammatory properties by affecting the secretion/expression of inflammation-related factors/genes. Therefore, VR-12 may be a good option for both warding off and treatmenting peri-implantitis.