Search Results (4,501)

The growing problem of antimicrobial resistance in aquaculture, caused by the excessive and unregulated use of antibiotics, highlights the critical necessity for developing new anti-infective solutions. Based on the characteristics of glycine-rich antimicrobial peptides (AMPs) and transcriptomic data, an antimicrobial peptide, namely AfRgly1, was discovered in this study. Subsequently, the peptide was obtained through heterologous expression in E. coli, and its antibacterial spectrum was determined. Molecular dynamics simulation and molecular biology experiments were conducted to explore the antibacterial target of AfRgly1. Results showed that the mRNA expression level of AfRgly1 was significantly upregulated after Vibrio alginolyticus infection. AfRgly1 has broad-spectrum antibacterial activity targeting on bacterial cell membrane, and it may also interact with bacterial DNA. AfRgly1 displayed low selectivity for fish red blood cells. These results indicate that AfRgly1 is an antimicrobial peptide with considerable potential for application in the development of therapeutic agents. Full article

Helicobacter pylori infection, a leading cause of gastric ulcers and gastric cancer, presents a major health challenge, exacerbated by rising antibiotic resistance. This study investigated the antibacterial potential of plant-derived compounds, isolated from different plant species, against H. pylori. Thus, a library of 153 natural compounds and derivatives, including monoterpene indole and bisindole alkaloids, obtained from the African medicinal plant Tabernaemontana elegans was screened in vitro for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against H. pylori. Active compounds (1-7) were tested for anti-biofilm activity and cytotoxicity on VERO cells to determine their half-maximal cytotoxic concentrations (CC₅₀). Six monoterpene indole alkaloid azine derivatives (1-6) and vobasinyl-iboga type bisindole alkaloid (7) displayed antibacterial activity, with MICs between 10 and 20 µM. Compounds 2, 3, and 6 exhibited bactericidal activity, with MBCs of 20 µM. Notably, compounds 1 to 4 inhibited H. pylori biofilm formation at sub-inhibitory concentrations. Cytotoxicity assays revealed CC₅₀ values above MICs, indicating a favorable safety profile for potential therapeutic use. This study highlights the potential of T. elegans monoterpene indole alkaloids as antibacterial agents and supports further exploration of plant-derived compounds as alternative treatments for H. pylori, offering a promising approach to address antibiotic resistance in gastrointestinal diseases. Full article

Endophytes are important sources of bioactive secondary metabolites with therapeutic and agricultural relevance. This study reports the isolation and characterization of bioactive compounds from endophytic Fusarium solani associated with Solanum surattense. The fungal strain, selected after preliminary screening for its antimicrobial potential, was identified through morphological and molecular methods. A pure compound, 4-hydroxyphenyl 8-chlorooctanoate with a molecular mass of 270, was obtained and structurally characterized using GC–MS, FTIR, and NMR spectroscopy. Its anti-microbial potential was evaluated through molecular docking against key bacterial (Staphylococcus aureus) and fungal (Aspergillus fumigatus) targets, showing notable binding affinities with ClpP protease (−7.1 kcal/mol) and 14α-demethylase (−7.4 kcal/mol), respectively. Molecular dynamics simulations further confirmed the stability of the 5FRB-compound complex, with lower RMSD and RMSF values indicating strong structural integrity. Supporting analyses (B-factor and radius of gyration) confirmed the compactness and rigidity of the complex. These findings highlight the potential of 4-hydroxyphenyl 8-chlorooctanoate as a promising antimicrobial agent and provide a strong basis for further in vitro and in vivo validation of the purified compound as an antimicrobial candidate. Full article

The rise of multidrug-resistant pathogens has become a serious health concern, creating an urgent need for novel therapeutic approaches. Among the compounds explored, AMPs have emerged as promising candidates due to their broad-spectrum activity and low propensity for resistance development. However, their clinical implementation is limited by improper size, in vivo instability, and toxicity. Here, we designed short analogs of CeHS-1 via (1) truncation of intact CeHS-1, (2) amino acid substitution, (3) end-tagging, and (4) C-terminal amidation. The results showed that short analogs fused with an RWW stretch exhibited stronger antibacterial activity than the parent analogs, without inducing hemolysis in human red blood cells. Among the tested AMPs, mechanistic studies revealed membrane-disruptive activity of certain peptides against Staphylococcus aureus. In silico analyses also suggested that the analogs bind DNA by aligning parallel to its grooves, where the RWW stretch is believed to contribute to interactions between arginine and tryptophan residues and nitrogenous bases through electrostatic, hydrogen bonding, and hydrophobic interactions. The short CeHS-1 analogs established here may serve as potential alternative antimicrobial agents, which should be tested in clinical trials in the future. Full article

Background: The bacterial wilt of tomatoes, caused by Ralstonia solanacearum, is a soil-borne plant disease that causes substantial agricultural economic losses. Various nanoparticles have been utilized as antibacterial agents to mitigate pathogenic destructiveness and improve crop yields. However, there is a lack of in-depth research on how nanoparticles affect tomato metabolite levels to regulate the bacterial wilt of tomatoes. Methods: In this study, healthy and bacterial wilt-infected tomatoes were treated with Cu-Ag nanoparticles, and a metabolomics analysis was carried out. Results: The results showed that Cu-Ag nanoparticles had a significant prevention and control effect on the bacterial wilt of tomatoes. Metabolomic analysis revealed that the nanoparticles could significantly up-regulate the expression levels of terpenol lipids, organic acids, and organic oxygen compounds in diseased tomatoes, and enhance key metabolic pathways such as amino acid metabolism, carbohydrate metabolism, secondary metabolite metabolism, and lipid metabolism. These identified metabolites and pathways could regulate plant growth and defense against pathogens. Correlation analysis between the tomato microbiome and metabolites showed that most endophytic microorganisms and rhizospheric bacteria were positively correlated with fatty acyls groups and organic oxygen compounds. Conclusions: This study reveals that Cu-Ag nanoparticles can actively regulate the bacterial wilt of tomatoes by up-regulating the levels of lipid metabolism and organic oxygen compounds, providing an important theoretical basis for the application of nanoparticles in agriculture. Full article

Bacterial infection is a cause of life-threatening diseases. The emergence of antimicrobial-resistant bacteria exacerbates this situation, highlighting the need for the discovery of new antimicrobial agents. Our previous study identified a novel antimicrobial peptide, BrSPR20-P1 (P1), which showed potential activity against MRSA. Additionally, silver nanoparticles (AgNPs) exhibit broad-spectrum antibacterial activity, capable of killing multidrug-resistant bacteria. The combination of antimicrobial agents presents a novel strategy for combating these pathogens. This study aimed to evaluate the antibacterial activity of the combination of P1 and AgNPs. It revealed that the combinations showed synergy. The P1 and AgNP mixture at a concentration of 1 and 8 µg/mL (1:8) doubled the activity against S. aureus and MRSA, while that combination of 64 and 64 µg/mL (64:64) exhibited broad-spectrum activity, expanding to E. coli with a 32-fold increase. These combinations exhibited a bactericidal effect, showing the rapid killing of tested bacteria at 10× MIC, with killing rates during the first 3 h ranging from 4.04 ± 0.01 to 4.31 ± 0.03 h⁻¹. The P1 and AgNP mixtures caused a low risk of antibacterial resistance up to 30 passages. It was demonstrated that the synergistic activity of P1 and AgNPs occurred through the disruption of cell walls and membranes, leakage of intracellular materials, and cell lysis. Additionally, the mixtures appeared to interact with bacterial genomic DNA, as indicated by a gel retardation assay. These activities of the combinations were concentration-dependent. The 1:8 µg/mL mixture caused low hemolysis and cytotoxicity and did not impede the wound healing process. In contrast, although the 64:64 µg/mL mixture showed excellent antibacterial efficacy, it was toxic to erythrocytes and mammalian cells. It implies that dose optimization is required to balance its efficacy and toxicity. Therefore, the P1 and AgNP combinations exhibit synergistic antimicrobial activity and have the potential to resolve bacterial infections. Full article

Chitosan is a natural biopolymer with intrinsic antimicrobial properties and strong metal ion chelating properties, making it an ideal matrix for the development of bioactive composites. In this study, silver and copper nanoparticles were synthesized using laser ablation in liquid (LAL) by the ablation of metallic targets into commercial chitosan (Cs) and chitosan produced from Hermetia illucens pupal exuviae (CsE) solutions, avoiding the use of chemical precursors or stabilizing agents. The nanocomposites obtained were characterized by UV–vis spectroscopy, TEM microscopy and FTIR spectroscopy in order to evaluate the size of the nanoparticles and the interactions between the polymer and metal nanoparticles. Antibacterial tests demonstrated the efficacy of Ag-based composites with a minimum inhibitory concentration (MIC) of 0.006 g/L, and Cu-based composites with a MIC of 0.003 g/L against both Escherichia coli and Micrococcus flavus. While the silver composites show antibacterial activity in both colloidal and film forms, the copper composites present antibacterial activity only in colloidal form. Swelling tests indicated that all films maintained a high water absorption capacity, with a swelling index over 200%, unaffected by nanoparticle integration. The results highlight the potential of LAL-synthesized metal–chitosan composites, particularly those based on insect chitosan, as sustainable and effective antimicrobial materials for biomedical and environmental applications. Full article

Biodegradable poly(lactic acid) (PLA)/poly(ε-caprolactone) (PCL) composite films were prepared with a compatibilizer (tributyl citrate, TBC) using a solvent casting method. Incorporation of 5% TBC (w/v, of PCL weight) improved tensile strength and elongation at break (21.93 ± 2.33 MPa and 21.02 ± 1.54%, respectively) and reduced water vapor permeability (from 0.12 ± 0.01 to 0.098 ± 0.01 g·mm·m²·h·kPa), indicating improved compatibility between PLA and PCL. Staphylococcus aureus phage PBSA08 demonstrated rapid and persistent bacteriolytic activity for up to 24 h, suggesting its potential as a promising antibacterial biological agent. To impart antibacterial properties to the developed PLA/PCL/TBC film, PBSA08 was loaded into sodium alginate (SA) and coated on the film surface. The optimal composition was 3% (w/v) SA and 3% (w/v) glycerol, which exhibited suitable dynamic behavior as a coating solution and excellent adhesion to the film surface. The phage-coated antibacterial films demonstrated progressive and significant inhibition against S. aureus starting from 10 to 24 h, with controlled phage-release properties. Overall, the developed active film might exert sustained and remarkable antibacterial effects through controlled release of biological agents (phage) under realistic packaging conditions. Full article

This study presents the results of a study of the synthesis and properties of 2-hydroxy-β-cyclodextrin functionalized by silver nanoparticles and its loading with a bioactive component. As a reducing agent and stabilizer, 2-Hydroxy-β-cyclodextrin (2gβCD) was used in the production of silver nanoparticles. The use of 2gβCD-AgNPs in loading molecules of the plant alkaloid lupinine (Lup) and its acetyl derivative (Lac) with bactericidal properties were studied. The formation of Lup-2gβCD-AgNPs and Lac-2gβCD-AgNPs was confirmed by UV spectroscopy and X-ray diffraction spectroscopy (XRD). Transmission electron microscopy (TEM) showed that the synthesized AgNPs had a spherical shape. ¹H-, ¹³C-NMR nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy (FT-IR) confirmed the reduction and encapsulation of AgNPs by 2gβCD. Thermographic data show that the obtained Lup and its derivative inclusion complexes reduced energy barriers. This makes them promising components for thermosensitive functional materials. Encapsulated complexes of Lup and its acetate inclusion with silver nanoparticles demonstrated significantly (p < 0.05) higher antibacterial, cytotoxic, and moderately pronounced analgesic activity. Full article

The phytochemical profiles, antioxidant capacities, mineral composition, and antibacterial activities of Zingiber officinale (Z. officinal) and Piper nigrum (P. nigrum) were explored through aqueous, ethanolic, and methanolic extractions. The extracts were analyzed for polyphenols, flavonoids, and tannins, and their antioxidant potential was assessed using the DPPH assay. UPLC-HRMS identified major bioactive compounds, including 6-gingerol and shogaol in Z. officinale, and piperine and piperlonguminine in P. nigrum. Mineral analysis showed that P. nigrum was particularly rich in essential elements, including calcium (Ca), magnesium (Mg), and iron (Fe). In antibacterial testing, P. nigrum demonstrated wider zones of inhibition against E. coli, whereas Z. officinale was more active at lower concentrations, showing MICs as low as 3.91 µg/mL against Salmonella and S. aureus. PCA analysis revealed strong correlations between phenolic content and biological effects. These results underscore the potential of both spices as effective natural agents for use in food preservation and health-promoting applications. Full article

Plants are a valuable source of bioactive compounds with therapeutic potential. Antibacterials of natural origin represent a promising and sustainable alternative in the fight against bacterial infections. In addition to being effective against bacterial growth, these natural agents may have lower toxicity and fewer side effects, which reinforces their value in the development of new therapeutic strategies. This study reports on the antibacterial effect of eugenol (EUG) and biogenic silver nanoparticles (bioAgNPs) synthesized using the aqueous extract of Trichilia catigua A. Juss. bark, alone or in combination, against planktonic and sessile cells of multidrug-resistant Staphylococcus pseudintermedius, one of the main opportunistic pathogens in dogs. EUG and bioAgNPs showed a dose- and time-dependent bactericidal effect on planktonic cells, interfering with cell membrane integrity. The interaction between EUG and bioAgNPs was classified as synergistic or indifferent for planktonic cells. Except for one isolate, the combination exhibited a synergistic effect for biofilms previously formed on abiotic surfaces for 24 h. Both bioactive compounds promoted morphological and ultrastructural changes in S. pseudintermedius biofilms. All concentrations of EUG and bioAgNPs in synergistic or indifferent combinations showed reduced toxicity to mammalian cells. These findings suggest that the EUG and bioAgNP combination could be a promising strategy for controlling S. pseudintermedius infections. Full article

Escherichia coli biofilms are implicated in the development of persistent infections and increased antibiotic resistance, posing a significant challenge in clinical settings. These biofilms enhance bacterial survival by forming protective extracellular matrices, rendering conventional treatments less effective. Serrapeptase (SPT), a proteolytic enzyme, has emerged as a potential anti-biofilm agent due to its ability to degrade biofilm components and disrupt bacterial adhesion. In this study, we report the inhibitory effect of SPT against E. coli biofilm and its effect on key virulence factors. In vitro assays, including crystal violet staining, optical and fluorescence microscopy, and viability measurements, revealed the dose-dependent inhibition of biofilm formation (IC₅₀ = 14.2 ng/mL), reduced biofilm (−92%, 500 ng/mL) and planktonic viability (−45%, 500 ng/mL), and a marked loss of amyloid curli fibers. SPT treatment also lowered the levels of key virulence factors: cellular and secreted lipopolysaccharides (−76%, 8 ng/mL; −94%, 32 ng/mL), flagellin (−63%, 8 ng/mL), and peptidoglycan (−29%, 125 ng/mL). Mechanistically, SPT induced a phosphate-dysregulating response: secreted alkaline phosphatase activity rose (+70%, 125 ng/mL) while cellular DING/PstS proteins declined (−84%, 64 ng/mL), correlating strongly with biofilm inhibition. In silico docking further suggests direct interactions between SPT and the curli subunits CsgA and CsgB, potentially blocking fiber polymerization. Together, these findings position SPT as a powerful non-antibiotic biofilm disruptor against E. coli, offering a promising strategy to undermine bacterial persistence and resistance by targeting both structural matrix components and metabolic regulatory pathways. Full article

The search for new antimicrobial agents is one of the major challenges in contemporary medicinal chemistry due to the global issue of increasing drug resistance. In our efforts to identify chemical structures with antibiotic activity that differ from commonly used antibiotics, we focused our research on (thio)semicarbazides and hydrazones. Guided by literature reports, we designed and synthesized a series of novel semicarbazides, thiosemicarbazides, and hydrazones based on the structure of 4-(morpholino-4-yl)-3-nitrobenzohydrazide. The obtained derivatives were subsequently evaluated in in vitro assays for their activity against reference strains of Gram-positive and Gram-negative bacteria. Among the studied groups of compounds, the semicarbazide derivatives exhibited the highest activity. The most active compound identified in the study was a semicarbazide containing a 4-bromophenyl moiety. This compound showed antibacterial potential against Enterococcus faecalis, with a MIC value of 3.91 µg/mL. Among the thiosemicarbazides, the most active compound contained a 4-trifluoromethylphenyl group, with MIC values against Gram-positive bacterial strains (excluding Staphylococcus aureus) ranging from 31.25 to 62.5 µg/mL. None of the tested hydrazones exhibited antimicrobial activity against the examined bacteria. Additionally, the structures of the new compounds were confirmed by single-crystal X-ray analysis, which enabled the investigation of their properties using advanced quantum chemical calculations. Full article

Antimicrobial materials are gaining significant interest as awareness of pathogens spread through contact becomes increasingly prevalent. While various compounds with antibacterial properties have been explored as active ingredients in such materials, many are prone to leaching, leading to undesirable risks to the environment and to human health. Herein, we develop and test a multilayered plastic film filled with silver nanoparticles, long known to be potent antibacterial agents, supported in a silica matrix. Cross-linked methacrylate layers on both sides of these nanostructures prevent leaching even after several uses, making the material essentially benign. Furthermore, we derive silica from rice husk, an abundant and affordable agricultural waste product. Our findings demonstrate that initial irradiation of the material with UVA light facilitates the photothermal migration of nanoparticles towards the material’s surface, thereby significantly enhancing its antimicrobial properties. Remarkably, after just 5 min of visible light irradiation, the material exhibits over 99.999% inhibition of bacterial growth. This environmentally friendly plastic composite harnesses visible light to actively combat bacteria, providing an exciting proof-of-concept for future applications in antimicrobial coatings. Full article

Background: The increasing number of resistant bacterial strains is reducing the effectiveness of antimicrobial drugs in preventing infections. It has been shown that resistant strains invade living organisms and cause a wide range of illnesses, leading to a surprisingly high death rate. Objective: The present study aimed to identify novel dihydropteroate synthase (DHPS) inhibitors from Stenotrophomonas maltophilia using structure-based computational techniques. Methodology: This in silico study used various bioinformatics and cheminformatics approaches to find new DHPS inhibitors. It began by retrieving the crystal structure via PDB ID: 7L6P, followed by energy minimization. The DHPS enzyme was virtually screened against the CHEMBL library to target S. maltophilia through enzyme inhibition. Then, absorption, distribution, metabolism, and excretion (ADME) analysis was performed to select the top hits. This process identified the top-10 hits. Additionally, imidazole (control) was used for comparative assessment. Furthermore, a 100 ns molecular dynamics simulation and post-simulation analyses were conducted. The docking results were validated through binding free energy calculations and entropy energy estimation approaches. Results: The docking results prioritized 10 compounds based on their binding scores, with a maximum threshold of −7 kcal/mol for selection. The ADME assessment shortlisted 3 out of 10 compounds: CHEMBL2322256, CHEMBL2316475, and CHEMBL2334441. These compounds satisfied Lipinski’s rule of five and were considered drug-like. The identified inhibitors demonstrated greater stability and less deviation compared to the control (imidazole). The average RMSD stayed below 2 Å, indicating overall stability without major deviations in the DHPS–ligand complexes. Post-simulation analysis assessed the stability and interaction profiles of the complexes under physiological conditions. Hydrogen bonding analysis showed the control to be more stable than the three tested complexes. Increased salt bridge interactions suggested stronger electrostatic stabilization, while less alteration of the protein’s secondary structure indicated better structural compatibility. These findings support the potential of these novel ligands as potent DHPS inhibitors. Binding energy estimates showed that CHEMBL2322256 was the most stable, with scores of −126.49 and −124.49 kcal/mol. Entropy calculations corroborated these results, indicating that CHEMBL2322256 had an estimated entropy of 8.63 kcal/mol. Conclusions: The newly identified compounds showed more promising results compared to the control. While these compounds have potential as innovative drugs, further research is needed to confirm their effectiveness as anti-DHPS agents against antibiotic resistance and S. maltophilia infections. Full article