Search Results (2,419)

Background: The growing interest in developing new bioactive agents from natural sources led to medicinal and aromatic plants. These plants provide valuable phytochemicals that can serve as natural preservatives, food additives, and flavorings, with various applications. The aim of this study is to evaluate the potential of Juniperus oxycedrus berries’ supercritical extract through preliminary screenings related to in vitro antibacterial activity, as well as bioinformatics assessments of absorption and toxicity. Methods: Supercritical carbon dioxide (CO₂) was used to extract the bioactive phytochemical compounds from the berries. The extract was characterized using spectrophotometric methods and reverse-phase high-performance liquid chromatography (RP-HPLC). The antibacterial potential was tested against Staphylococcus aureus ATCC 25923, where the Minimal Inhibitory Concentration and the Minimal Bactericidal Concentration were determined. Additionally, the influence of the extract on the growth curve kinetics of S. aureus was assessed. For the bioinformatics analyses, SwissADME and ProTox-3.0 prediction software were utilized, focusing on the identified phenolic compounds as fingerprint molecules. Results: The results demonstrated that exposure to the juniper extract inhibited bacterial growth, resulting in a prolonged lag phase of 6 to 8 h, depending on the concentration of the extract. The software predictions revealed that the investigated phenolic compounds might exhibit high gastrointestinal absorption, along with potential interactions with metabolic mediators and pathways. Conclusions: The in vitro and in silico findings support the application of J. oxycedrus berries extract as an alternative or complementary strategy for pharmacological treatment and food applications aimed at targeting S. aureus. Full article

The global spread of multidrug-resistant (MDR) Gram-negative bacteria, particularly extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, presents a significant public health challenge by limiting effective antimicrobial treatment options. Cefepime, a fourth-generation cephalosporin with broad-spectrum activity, is increasingly compromised by β-lactamase production, efflux pumps, and porin loss. In response, novel cefepime-based β-lactam/β-lactamase inhibitor (BL/BLI) combinations have been developed to overcome these resistance mechanisms. This review examines preclinical and clinical studies on cefepime-based BL/BLI combinations, specifically cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, and cefepime/nacubactam, as found in the PubMed database. Key findings include the restoration of activity against class A ESBLs with cefepime/enmetazobactam, while cefepime/taniborbactam and cefepime/zidebactam show broader inhibition of serine β-lactamases and selected metallo-β-lactamases. Additionally, zidebactam and nacubactam target penicillin-binding protein 2, enhancing bactericidal potency. Preclinical and early-phase clinical trial data indicate potent in vitro activity and favorable pharmacokinetic/pharmacodynamic (PK/PD) profiles. Specifically, the combination of cefepime with enmetazobactam has demonstrated an optimal Cmax/MIC ratio of 8–10, supporting its efficacy in treating MDR Gram-negative infections. Phase III studies are ongoing to confirm efficacy in complicated infections. Cefepime-based BL/BLI combinations are emerging as promising carbapenem-sparing agents, offering broad-spectrum activity, dual mechanisms of action, and encouraging clinical outcomes. These findings support their inclusion in antimicrobial stewardship strategies aimed at mitigating resistance. Full article

The microbiological safety of whole wheat flour remains a critical issue due to its susceptibility to contamination by spore-forming thermophilic bacteria. In this study, two thermophilic species, Bacillus subtilis and Bacillus mesentericus, were isolated from locally produced wheat grains and used as target microorganisms to evaluate the antibacterial potential of freshly pressed cabbage juices. Juices obtained from five cabbage varieties—red cabbage, white cabbage, napa (Chinese) cabbage, broccoli, and cauliflower—were comparatively assessed using the broth dilution method to determine their minimum inhibitory and bactericidal effects (n = 3). The results revealed pronounced differences in antibacterial efficacy among the tested samples. White cabbage juice exhibited selective inhibitory activity against B. subtilis at a dilution of 1:4, whereas napa cabbage and broccoli juices demonstrated the highest antibacterial activity against both Bacillus species at a dilution of 1:3. Importantly, napa cabbage juice showed no inhibitory effect on Saccharomyces cerevisiae, indicating its compatibility with dough fermentation processes. Spectroscopic analysis of the bioactive fraction obtained from napa cabbage juice revealed characteristic absorption bands at 3422 cm⁻¹ (O–H stretching), 2907–2840 cm⁻¹ (aliphatic C–H stretching), 1740 cm⁻¹ (ester carbonyl group), and 1641 cm⁻¹ (C=C stretching). The predominance of lipophilic compounds, including fatty acid esters, terpenes, and sulfur-containing compounds (734 cm⁻¹), suggests a molecular basis for the observed antibacterial activity against Bacillus spp. Overall, these findings identify napa cabbage as a promising source of selective natural antimicrobial agents capable of enhancing the microbiological safety of whole wheat flour-based bakery products without compromising yeast activity. Full article

Antimicrobial resistance is a major global health concern, intensified by the misuse of antibiotics and the lack of new effective treatments. Bacteria capable of forming biofilms exhibit increased resistance, making infections more difficult to treat. This study evaluated the essential oil from Croton pluriglandulosus leaves (OCp) for its antibacterial and antibiofilm properties. The essential oil, obtained by hydrodistillation and analyzed by GC-MS, contained eucalyptol (24.11%), spathulenol (16.90%), α-pinene (11.76%), and caryophyllene oxide (10.07%) as main constituents. Antibacterial activity was determined by Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC), with inhibition observed only for Staphylococcus aureus (MIC 10 mg/mL; MBC 5 mg/mL). OCp reduced biofilm biomass and CFUs in most strains, particularly in S. aureus and Escherichia coli. Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) showed membrane damage in treated cells. Overall, OCp displayed promising antibacterial and antibiofilm potential, representing the first report of such activity for this essential oil. Full article

Lactobionic acid (LBA) has demonstrated antibacterial activities against multiple foodborne bacteria; however, few studies have reported on its effect against Cronobacter sakazakii. In this study, the antibacterial activity and mode of LBA against C. sakazakii were explored. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of LBA against C. sakazakii were 12.5 and 25 mg/mL, respectively. LBA exhibited bacteriostatic activity at sub-MIC and bactericidal activity at concentrations ≥ MIC. Alkaline phosphatase (AKP) activity, cell outer membrane (OM) permeability, protein leakage, and gel electrophoresis results suggested that LBA increased the permeability of the cell wall and OM, leading to intracellular protein leakage and a decrease in protein contents and activity, indicating LBA damage to the cell wall and membrane. Among these, the rapid AKP activity surge reached 4.37 U/gprot at 2 MIC, and the OM permeability dramatically increased up to 10 min and stabilized after 30 min. Microscopic observations confirm the disruption to the cell wall and membrane, further showing that LBA disrupted the integrity of the cell wall and membrane. Moreover, LBA disturbs normal cellular functions by binding to deoxyribonucleic acid (DNA), as reflected by the competitive binding assay. Overall, LBA possesses potential multiple applications in the food industry due to its natural and antibacterial properties. Full article

The bactericidal permeability-increasing protein (BPI) and lipopolysaccharide binding protein (LBP) are fundamental to innate immunity. However, their functional diversity and evolutionary conservation in ecologically crucial invertebrates, such as oysters, remain largely understudied. In this study, we identify and characterize a novel homolog of BPI/LBP, designated as ChBPI/LBP in the Hong Kong oyster (Crassostrea hongkongensis). Through structural and phylogenetic analysis, we identify ChBPI/LBP as a distinct member of the BPI protein family, with a high isoelectric point (pI of 9.26), indicating potent cationic BPI-like bactericidal function. We found that ChBPI/LBP is constitutively highly expressed at mucosal sites such as the gills and is rapidly upregulated in hemocytes following a challenge with Aeromonas hydrophila. Recombinant ChBPI/LBP demonstrated potent and specific bactericidal activity against Gram-negative pathogens. These findings suggest that ChBPI/LBP is an important antimicrobial peptide (AMP) effector in the oyster’s immune response. This work provides novel perspectives on the evolutionary mechanisms of innate immunity in bivalves and may have implications for disease management in aquaculture. Full article

This study aimed to develop natural, safe, and effective antimicrobial packaging materials for extending the shelf life of chilled pork during refrigeration. Emodin-chitosan (Em-Cs) composite films with varied concentrations were developed by combining the casting method with photodynamic inactivation technology, utilizing chitosan as the matrix and emodin as the functional photosensitizer for active packaging. The optical, mechanical, and barrier properties of the composite films were examined. The inhibitory effects of the samples on Escherichia coli, Salmonella Derby, Staphylococcus aureus, and Pseudomonas fragi under 450 nm blue light irradiation were evaluated. The results demonstrated that the Em-Cs composite film exhibited excellent transparency, mechanical strength, and water barrier properties, with good compatibility between emodin and chitosan. Under light irradiation, the composite film generates reactive oxygen species (ROS), whose bactericidal efficacy depends on the concentration of emodin and the duration of light exposure. When applied to chilled pork packaging, this composite film inhibited bacterial growth within the meat for 10 days, effectively retarding pH increase, lipid oxidation, and volatile basic nitrogen accumulation. The present study proposes a novel methodology for the application of photodynamic technology in the context of food preservation, and it presents a new type of natural antimicrobial packaging material for the preservation of chilled pork. Full article

Vanadium carbide (V₂C) MXene shows great potential for addressing challenging implant-associated infections in bone regeneration due to its strong photothermal conversion efficiency. However, its photothermal efficacy is restricted to the near-infrared I (NIR-I) region due to a limited absorption range. To address this, we designed platinum nanoparticle-decorated V₂C heterostructures (Pt@V₂C) via an in situ growth method, leveraging Pt’s plasmonic and catalytic properties to extend the photoresponse to the NIR-II window. Subsequently, Pt@V₂C was integrated into poly-L-lactic acid (PLLA) to fabricate PLLA-Pt@V₂C scaffolds with photothermal antibacterial function by selective laser sintering. The optimized PLLA-Pt@V₂C scaffold achieves a record photothermal conversion efficiency (56.03% at 1064 nm), triggering simultaneous hyperthermia (>52 °C) and catalytic ·OH radical generation. In vitro studies demonstrate exceptional antibacterial efficacy against Staphylococcus aureus and Escherichia coli, achieving over 99% killing rates upon 1064 nm near-infrared irradiation. Furthermore, the scaffold demonstrated significant inhibition of biofilm formation, achieving over 90% reduction in biofilm biomass. Moreover, the scaffold demonstrated high cell viability, confirming its dual functionality of potent bactericidal activity and biocompatibility that supports tissue regeneration. This work provides a feasible strategy for combating implant-associated infections. Full article

Background/Objectives: Multidrug-resistant (MDR) strains of Streptococcus suis are increasingly prevalent and present significant challenges in clinical management. Given that the development of new antibiotics is a resource-intensive process and time-consuming, there is an urgent need for alternative therapeutic strategies to address resistance in the short term. One promising approach is the use of combination therapy, which involves pairing potent antibiotics with agents that may be less effective on their own, to enhance therapeutic efficacy and potentially overcome resistance mechanisms. This study aimed to investigate the in vitro antibacterial activity of combining two classes of antibiotics with distinct mechanisms of action—cell wall synthesis inhibitors and protein synthesis inhibitors—against MDR S. suis strains isolated from diseased pigs. Methods: A total of 36 MDR S. suis strains were tested using a microbroth dilution checkerboard assay to determine the minimum inhibitory concentration (MIC) of four cell wall synthesis inhibitors —amoxicillin/clavulanic acid (AMC), ampicillin (AMP), penicillin G (PEN), and vancomycin (VAN)— in combination with four protein synthesis inhibitors —gentamicin (GEN), neomycin (NEO), tilmicosin (TMS), and tylosin (TYL). Time–kill curve assays were conducted to evaluate the in vitro bactericidal activity of synergistic antibiotic combinations (PEN–GEN and AMP–NEO) against Beta-lactam-resistant and Beta-lactam-susceptible MDR S. suis strains. Results: Checkerboard analysis revealed that penicillin-gentamicin combination exhibited the most effective synergistic activity against the MDR S. suis strains (10/19, 52.6%), with ∑FIC values of 0.25–1.06 and MIC reductions from resistant to susceptible levels. Time-kill assays further confirmed the synergistic bactericidal effect of the combination, demonstrating complete bacterial clearance within 6–9 h, markedly rapid bacterial killing compared to monotherapy. Conclusions: This study demonstrates that antibiotic combinations, particularly Beta-lactams combined with aminoglycosides, show synergistic activity against pig-isolated S. suis MDR strains. The PEN-GEN combination exhibited strong synergistic and bactericidal effects, supporting combination therapy as a potential strategy to address antimicrobial resistance. Further evaluation in diverse strain backgrounds and prudent antibiotic use are essential to confirm efficacy and limit the emergence of antibiotic resistance. Full article

The increasing crisis of antimicrobial resistance requires innovative therapeutic strategies that can overcome the limitations of conventional antibiotics. Based on our previous finding that AP10 (a derivative of AP29) possesses antimicrobial activity but lacks thermal stability, we rationally redesigned ten new AP10 analogues to enhance functional robustness while maintaining efficacy. Among these, AP10RW is identified as the optimal candidate due to its exceptional broad-spectrum activity against both drug-sensitive and multidrug-resistant (MDR) bacterial pathogens. Structural analysis reveals that AP10RW adopts an environmentally responsive conformation, transitioning from random coil to amphiphilic α-helix in membrane-mimicking environments, while demonstrating remarkable stability under challenges including serum exposure, varying pH, high salt concentrations, and thermal stress. Mechanistic studies indicate that AP10RW exerts its effects through multiple bactericidal mechanisms involving initial high-affinity binding to bacterial characteristic molecules (LTA, LPS and PGN), followed by rapid membrane depolarization, ultrastructural damage and the induction of lethal oxidative stress. Notably, this potent antimicrobial efficacy is coupled with exceptional biosafety, demonstrating little hemolysis and negligible cytotoxicity against mammalian cells. This systematic optimization represents a significant advancement in antimicrobial peptide engineering. We have successfully transformed a thermally unstable peptide into a robust therapeutic candidate and positioned AP10RW as a promising clinical candidate for addressing the growing threat of multidrug-resistant infections. Full article

Background/Objectives: Shigella is the leading bacterial cause of diarrheal disease worldwide. Although multiple vaccine candidates are under development and in clinical trials, no Shigella vaccine is currently available on the market. Shigella comprises four species: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. S. flexneri has been recognized as the most prevalent species, particularly in low- and middle-income countries (LMICs), and the top serotypes are S. flexneri 2a, 3a and 6. Conversely, S. sonnei has a single serotype and predominates in high-income countries (HICs). Invasion plasmid antigen B (IpaB) is a critical virulence factor of Shigella type III secretion system (T3SS) that is highly conserved across Shigella serotypes. Here, we report the development of a Shigella quadrivalent O-polysaccharide-IpaB conjugate vaccine candidate (IVT Shigella-04). Methods: IVT Shigella-04 contains O-polysaccharides (O-PS) from S. flexneri 2a, 3a, 6, and S. sonnei, each individually conjugated to recombinantly expressed IpaB as the carrier protein using 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) chemistry. The immunogenicity of IVT Shigella-04 was evaluated in a rabbit immunization model. Results: Baseline (day 0) IgG concentrations were low for all four Shigella serotypes (<0.5 µg/mL). Following two doses on day 0 and day 28 (2.5 µg of each conjugate per dose; total 10 µg), IgG geometric mean concentrations increased significantly (p < 0.001) by day 42, reaching 67.96 µg/mL (2a), 91.56 µg/mL (3a), 371.31 µg/mL (6), and 11.00 µg/mL (sonnei). Consistently, serum bactericidal activity (SBA) at day 42 increased 13-fold (2a), 34-fold (3a), 63-fold (6), and 224-fold (sonnei) relative to baseline (day 0). Conclusions: IVT Shigella-04 elicited robust serotype-specific humoral and functional immune responses in preclinical models, supporting its further development toward clinical evaluation. Full article

Background: Streptococcus pneumoniae (Spn) is a leading bacterial pathogen responsible for severe invasive diseases, including meningitis, sepsis, and pneumonia. Current pneumococcal vaccines, which are all based on capsular polysaccharide antigens, provide limited protection and are further compromised by post-vaccination serotype replacement. Pneumococcal surface protein A (PspA), a highly conserved virulence factor expressed across diverse serotypes, has emerged as a promising candidate antigen for novel protein-based vaccines. However, progress in this field has been hindered by the absence of standardized in vitro functional antibody assays. Methods: This study established a robust functional antibody detection method for PspA-based protein vaccines by modifying the conventional multiplex opsonophagocytic killing assay (MOPA), originally designed for polysaccharide-based vaccines. Using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) typing, a target strain panel was selected and developed to include representative strains from PspA Family 1-Clade 2 and Family 2-Clades 3 and 4. The MOPA protocol was optimized by extending the phagocytic reaction time to enhance sensitivity. Specificity was confirmed through recombinant PspA competitive inhibition assays. Results: The assay demonstrated high linearity (R² ≥ 0.98) between opsonophagocytic index (OI) and serum dilution, along with acceptable repeatability (CV ≤ 30%) and intermediate precision (CV ≤ 50%). Both preclinical and clinical serum samples exhibited potent bactericidal activity against diverse PspA families, independent of capsule type. Conclusions: This study provided a standardized framework to support the development and regulatory assessment of protein-based pneumococcal vaccines. Full article

Lower respiratory tract infections caused by Pseudomonas aeruginosa are a global concern. Patients with chronic lung diseases such as cystic fibrosis and non-cystic fibrosis bronchiectasis often do not receive adequate antibiotic delivery through conventional routes. P. aeruginosa employs several mechanisms, including biofilm formation and efflux pumps to limit the accumulation of bactericidal drug concentrations. Direct drug delivery to the lung epithelial lining fluid can increase antibiotic concentration and reduce treatment failure rates. This review discusses current research and developments in inhaled antibiotic formulations for treating P. aeruginosa infections. Recent studies on particle engineering for the dry powder inhalers of antibiotics emphasized three fundamental principles of development: micro, nano, and nano-in-microparticles. Carrier-free microparticles showed potential for high-dose delivery but suffered from poor aerosolization, which could be improved through a drug–drug combination. Amino acids in a co-spray-dried system improved powders’ aerodynamics and reduced moisture sensitivity while incorporating the chitosan/poly(lactic-co-glycolic acid) (PLGA)-modified release of the drug. Nano-in-microsystems, embedding lipid carriers, showed improved antibiofilm activity and controlled release. We also highlight emerging biologics, including antibacterial proteins/peptides, vaccines, bacteriophages, and probiotics. Research on antibiotics and biologics for inhalation suggests excellent safety profiles and encouraging efficacy for some formulations, including antimicrobial peptides and bacteriophage formulations. Further research on novel molecules and synergistic biologic combinations, supported by comprehensive animal lung safety investigations, will be required in future developments. Full article

Due to the indiscriminate use of antimicrobial drugs in the treatment of infectious diseases, human pathogenic bacteria have developed resistance to many commercially available antibiotics. Medicinal plants such as Convolvulus arvensis represent a renewable resource for the development of alternative therapeutic agents. This study aimed to evaluate the antibacterial activity of silver nanoparticles (AgNPs) biosynthesized from C. arvensis against two clinical antibiotic-resistant bacterial isolates. The pathogenic isolates were identified as Staphylococcus aureus MRSA and Escherichia coli ESBL using 16S rRNA gene sequencing. Silver nanoparticles were synthesized via a green synthesis approach, and their physicochemical properties were characterized using UV–Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, zeta potential, and dynamic light scattering (DLS). The synthesized C. arvensis–AgNPs exhibited a surface plasmon resonance peak at 475 nm and predominantly spherical morphology with particle sizes ranging from 102.34 to 210.82 nm. FTIR analysis indicated the presence of O–H, C–O, C–N, C–H, and amide functional groups. The nanoparticles showed a zeta potential of −18.9 mV and an average hydrodynamic diameter of 63 nm. The antibacterial activity of the biosynthesized AgNPs was evaluated against methicillin-resistant S. aureus (MRSA and ATCC 29213) and E. coli (ESBL and ATCC 25922) using agar diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays. Inhibition zones ranged from 10 to 13 mm, with MIC and MBC values of 12.5–25 µg/mL and 25–50 µg/mL, respectively. In addition, the nanoparticles exhibited antioxidant activity (DPPH assay, IC₅₀ = 0.71 mg/mL) and anti-inflammatory effects as determined by protein denaturation inhibition. No cytotoxic effects were observed in the MCF-7 cell line at the MIC level. These findings suggest that C. arvensis–AgNPs have potential as natural antimicrobial, antioxidant, and anti-inflammatory agents. Full article

This study reports the fabrication of chitosan/carboxymethyl cellulose (C/M) nanocomposites by electrolyte gelation–spray drying and the evaluation of their antibacterial performance as carriers for the antibiotic ampicillin. Chitosan (C), a cationic biopolymer derived from chitin, was combined with the anionic polysaccharide carboxymethyl cellulose (M) at different mass ratios to form stable nanocomposites via electrostatic interactions and then collected in a spray dryer. The resulting particles exhibited mean diameters ranging from 800 to 1500 nm and zeta potentials varying from +90 to −40 mV, depending on the C/M ratio. The optimal formulation (C/M = 2:1 ratio) achieved a high recovery yield (71.1%), lower PDI (0.52), and ampicillin encapsulation efficiency EE (82.4%). Fourier transform infrared spectroscopy (FTIR) confirmed the presence of hydrogen bonding and ionic interactions among C/M, and ampicillin within the nanocomposite matrix. The nanocomposites demonstrated controlled ampicillin release and pronounced antibacterial activity against Staphylococcus aureus, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 3.2 µg/mL and 5.3 µg/mL, respectively, which were lower than those of free ampicillin. These results indicate that the chitosan/carboxymethyl cellulose nanocomposites are promising, eco-friendly carriers for antibiotic delivery and antibacterial applications. Full article