Search Results (471)

Cystic fibrosis produces viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in cystic fibrosis patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX), which functions to inhibit bacterial replication but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled therapy due to enhanced targeting and delivery. The extracellular matrix (ECM) has been shown to possess pro-regenerative and non-toxic properties in vitro, making it a promising delivery agent. The combination of LVX and ECM formed into nanoparticles may overcome barriers to lung delivery to effectively treat cystic fibrosis bacterial infections. Our goal is to advance CF care by providing a combined treatment option that has the potential to address both bacterial infections and lung damage. Two hybrid formulations of a 10:1 and 1:1 ratio of LVX to ECM have shown neutral surface charges and an average size of ~525 nm and ~300 nm, respectively. The neutral charge and size of the particles may suggest their ability to attract toward and penetrate through the mucus barrier in order to target the bacteria. The NPs have also been shown to slow the drug dissolution, are non-toxic to human airway epithelial cells, and are effective in inhibiting Pseudomonas aeruginosa and Staphylococcus aureus. LVX-ECM NPs may be an effective treatment for pulmonary CF bacterial treatments. Full article

Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) designed for the sustained release of vancomycin hydrochloride. Methods: The MPs were co-loaded with indocyanine green (ICG), a near-infrared (NIR) responsive agent, and fabricated via the double emulsion method.They were characterized for stability, surface modification, biocompatibility, and antibacterial efficacy. Results: Dynamic light scattering and zeta potential analyses confirmed significant increases in particle size and surface charge reversal following chitosan coating. Scanning electron microscopy revealed uniform morphology in uncoated MPs (1–10 $\mathsf{\mu }$m) and irregular surfaces post-coating. Stability tests demonstrated drug retention for up to 180 days. Among formulations, PVI1 exhibited the highest yield (76.67 ± 1.3%) and encapsulation efficiency (56.2 ± 1.95%). NIR irradiation (808 nm) enhanced drug release kinetics, with formulation PVI4 achieving over 48.9% release, resulting in improved antibacterial activity. Chitosan-coated MPs (e.g., PVI4-C) effectively suppressed drug release without NIR light for up to 8 h, with cumulative release reaching only 10.89%. Without NIR light, bacterial colonies exceeded 1000 CFU; NIR-triggered release reduced them below 120 CFU. Drug release data fitted best with the zero-order and Korsmeyer–Peppas models, suggesting a combination of diffusion-controlled and constant-rate release behavior. Conclusions: These results demonstrate the promise of chitosan-coated NIR-responsive PLGA MPs for precise, on-demand antibiotic delivery and improved antibacterial performance. Full article

Background: Peptides are a class of molecules that can be presented as good antimicrobials and with mechanisms that avoid resistance, and the design of peptides with good activity can be complex and laborious. The study of their quantitative structure–activity relationships through machine learning algorithms can shed light on a rational and effective design. Methods: Information on the antimicrobial activity of peptides was collected, and their structures were characterized by molecular descriptors generation to design regression and classification models based on machine learning algorithms. The contribution of each descriptor in the generated models was evaluated by determining its relative importance and, finally, the antimicrobial activity of new peptides was estimated. Results: A structured database of antimicrobial peptides and their descriptors was obtained, with which 56 machine learning models were generated. Random Forest-based models showed better performance, and of these, regression models showed variable performance (R² = 0.339–0.574), while classification models showed good performance (MCC = 0.662–0.755 and ACC = 0.831–0.877). Those models based on bacterial groups showed better performance than those based on the entire dataset. The properties of the new peptides generated are related to important descriptors that encode physicochemical properties such as lower molecular weight, higher charge, propensity to form alpha-helical structures, lower hydrophobicity, and higher frequency of amino acids such as lysine and serine. Conclusions: Machine learning models allowed to establish the structure–activity relationships of antimicrobial peptides. Classification models performed better than regression models. These models allowed us to make predictions and new peptides with high antimicrobial potential were proposed. Full article

This work presents the synthesis, characterization and evaluation of physicochemical and biological properties of two new aminoporphyrazine derivatives bearing magnesium(II) cations in their cores and peripheral pyrrolyl groups. The synthesis was carried out in several stages, using classical methods and the Microwave-Assisted Organic Synthesis (MAOS) approach. The obtained compounds were characterized using spectral techniques: UV-Vis spectrophotometry, mass spectrometry, ¹H and ¹³C NMR spectroscopy. The porphyrazine derivatives were tested for their electrochemical properties (CV and DPV), which revealed four redox processes, of which in compound 7 positive shifts of oxidation potentials were observed, resulting from the presence of free phenolic hydroxyl groups. In spectroelectrochemical measurements, changes in UV-Vis spectra associated with the formation of positive-charged states were noted. Photophysical studies revealed the presence of characteristic absorption Q and Soret bands, low fluorescence quantum yields and small Stokes shifts. The efficiency of singlet oxygen generation (Φ_Δ) was higher for compound 6 (up to 0.06), but compound 7, despite its lower efficiency (0.02), was distinguished by a better biological activity profile. Toxicity tests using the Aliivibrio fischeri bacteria indicated the lower toxicity of 7 compared to 6. The most promising result was the strong photodynamic activity of porphyrazine 7 against the Methicillin-resistant Stapylococcus aureus (MRSA) strain, leading to a more-than-5.6-log decrease in viable counts after the colony forming units (CFU) after light irradiation. Compound 6 did not show any significant antibacterial activity. The obtained data indicate that porphyrazine 7 is a promising candidate for applications in photodynamic therapy of bacterial infections. Full article

This study presents a quantitative electrophysiological method to directly measure the passive transport of ammonium ions through bacterial outer membrane porins. Using a zero-current reversal potential assay in planar lipid bilayers under defined bi-ionic gradients, this study evaluates the permeability of ammonium salts through two general diffusion porins: Omp-Pst2 from Providencia stuartii and OmpF from Escherichia coli. Under matched ionic conditions, Omp-Pst2 exhibited significantly higher ammonium flux—approximately 6000 ions per second per monomer at a 1 µM gradient—compared to ~4000 ions per second for OmpF. Importantly, the identity of the accompanying anion (chloride vs. sulfate) modulated both the ion selectivity and flux rate, highlighting the influence of counterion interactions on porin-mediated transport. These findings underscore how structural differences between porins—such as pore geometry and charge distribution—govern ion permeability. The method applied here provides a robust framework for quantifying nutrient flux at the single-channel level and offers novel insights into how Gram-negative bacteria may adapt their membrane transport mechanisms under nitrogen-limited conditions. This work not only enhances our understanding of outer membrane permeability to small ions like ammonium, but also has implications for antimicrobial strategy development and biotechnological applications in nitrogen assimilation. Full article

The increasing resistance of pathogenic microorganisms to antimicrobials has driven the search for safe and sustainable alternatives. In this context, microbial biosurfactants have gained prominence due to their antimicrobial activity, low toxicity, and high stability under extreme conditions. This study presents the production and characterization of a biosurfactant with antimicrobial potential, obtained from Bacillus subtilis isolated from soil, for application in the control of resistant strains. Bacterial identification was performed using mass spectrometry (MALDI-TOF), confirming it as Bacillus subtilis. The strain B. subtilis UCP 1533 was cultivated using different carbon sources (glucose, soybean oil, residual frying oil, and molasses) and nitrogen sources (ammonium chloride, sodium nitrate, urea, and peptone), with evaluations at 72, 96, and 120 h. The best condition involved a mineral medium supplemented with 2% soybean oil and 0.12% corn steep liquor, resulting in the production of 16 g·L⁻¹ of biosurfactant, with a critical micelle concentration (CMC) of 0.3 g·L⁻¹ and a reduction in water surface tension to 25 mN·m⁻¹. The biosurfactant showed an emulsification index of 100% for used motor oil and ranged from 50% to 100% for different vegetable oils, maintaining stability across a wide range of pH, salinity, and temperature. FT-IR and NMR analyses confirmed its lipopeptide nature and anionic charge. Toxicity tests with Tenebrio molitor larvae showed 100% survival at all the tested concentrations. In phytotoxicity assays, seed germination rates above 90% were recorded for Solanum lycopersicum and Lactuca sativa. Antimicrobial tests revealed inhibitory activity against resistant strains of Escherichia coli and Pseudomonas aeruginosa, as well as against species of the genus Candida (C. glabrata, C. lipolytica, C. bombicola, and C. guilliermondii), highlighting the biosurfactant as a promising alternative in combating antimicrobial resistance (AMR). These results indicate the potential application of this biosurfactant in the development of antimicrobial agents for pharmaceutical formulations and sustainable strategies for phytopathogen control in agriculture. Full article

Background/Objectives: Thymol, one of the main compounds of thyme essential oil, has shown promising effects in treating various skin disorders owing to its anti-inflammatory, antimicrobial and antioxidative activities. Due to its limited solubility in water, thymol is commonly used in higher concentrations to achieve a suitable therapeutic effect, which can consequently lead to skin irritation. To overcome these limitations, we incorporated thymol into a vesicular phospholipid gel (VPG), a novel semisolid dermal vehicle consisting of highly concentrated dispersion of phospholipid vesicles (liposomes). Methods: Thymol was successfully loaded into two VPGs differing in bilayer fluidity, which were characterized for the physicochemical and rheological properties, storage stability, in vitro release, ex vivo skin permeability, in vitro compatibility with epidermal cells, wound healing potential, and antibacterial activity against skin-relevant bacterial strains. Results: High pressure homogenization method enabled preparation of VPG-liposomes of neutral surface charge in the size range 140–150 nm with polydispersity indexes below 0.5. Both types of VPGs exhibited viscoelastic solid-like structures appropriate for skin administration and ensured skin localization of thymol. Although both types of VPGs enabled prolonged release of thymol, the presence of cholesterol in the VPG increased the rigidity of the corresponding liposomes and further slowed down thymol release. Conclusions: Loading of thymol into VPGs significantly reduced its cytotoxicity toward human keratinocytes in vitro even at very high concentrations, compared to free thymol. Moreover, it facilitated in vitro wound healing activity, proving its potential as a vehicle for herbal-based medicines. However, the antibacterial activity of thymol against Staphylococcus aureus and methicillin-resistant S. aureus was hindered by VPGs, which represents a challenge in their development. Full article

Background: Community-acquired bacterial pneumonia (CABP) is a common and costly cause of hospitalization. Although severe CABP (sCABP) occurs in 10–25% of all pneumonia hospitalizations, little generalizable data examine its characteristics and outcomes or hospital resource utilization. Methods: We conducted a retrospective single-group cohort study of adults within the IQVIA hospital Charge Data Master, 2018–2022. We identified CABP via an ICD-10 code algorithm and sCABP was defined as an episode requiring ICU care. We examined baseline characteristics and outcomes, including mortality, costs, and readmission rates. We developed models to identify risk factors associated with readmissions. Results: Among 24,149 patients with sCABP, 14,266 (58.4%) were ≥65 years old and 55.2% were male. The majority were hospitalized in large (300+ beds, 50.9%), urban (91.9%) teaching (62.7%) institutions in the US Southern region (52.3%). The mean (SD) Charlson Comorbidity Index was 1.35 (2.33). The most common comorbidities were hypertension (16.7%), diabetes mellitus (15.7%), and chronic obstructive pulmonary disease (COPD) (12.9%). Hospital mortality was 15.9%. The mean (SD) hospital length of stay (LOS) and costs were 13.6 (12.1) and USD 91,965 (USD 133,734), respectively. An amount of 20% required a readmission within 30 days. Readmission was most strongly associated with older age and the presence of select comorbidities (diabetes mellitus, congestive heart failure, and COPD), each with an odds ratio > 1.4 and 95% confidence intervals excluding 1.0. Conclusions: Patients with sCABP comprise a large population with high mortality and 30-day readmissions. The intrinsic factors related to the latter lend themselves to early recognition and aggressive efforts at reducing complications. Full article

Heparin, a widely used polysaccharidic anticoagulant of animal origin, is associated with risks of contamination and adverse effects, notably bleeding and thrombocytopenia. These limitations have prompted interest in alternative sulfated polysaccharides with anticoagulant properties and improved safety profiles. This study explored the anticoagulant potential of two marine bacterial exopolysaccharides (EPS), infernan and diabolican. It assessed whether chemical modifications (depolymerization, oversulfation) could enhance their anticoagulant properties compared to unfractionated and low molecular weight heparins. Native EPS were depolymerized to generate different molecular weights and then chemically oversulfated to increase negative charge density. Anticoagulant activities were evaluated using clotting and thrombin generation assays (TGA). Molecular docking was performed to model interactions with antithrombin and heparin cofactor II. Only highly sulfated derivatives significantly prolonged activated partial thromboplastin time while showing negligible effect on thrombin time and anti-factor Xa activity. They present different structures, and their binding to antithrombin is not achieved via the classic pentasaccharide motif. In TGA, these derivatives inhibited thrombin formation at higher doses than heparin but induced a marked delay in clot generation. Docking analyses supported their ability to bind serpins, albeit with lower specificity than heparin. Their limited anti-Xa activity and non-animal origin position them as promising anticoagulant candidates. Full article

The maritime shipping sector is a major contributor to greenhouse gas emissions, particularly in coastal regions. In response, the adoption of electric ferries powered by renewable energy and supported by battery storage technologies has emerged as a viable decarbonization pathway. This study investigates the operational impacts of coordinated electric ferry charging on a medium-voltage distribution network at Gladstone Marina, Queensland, Australia. Using DIgSILENT PowerFactory integrated with MATLAB Simulink and a Python-based control system, four proposed ferry terminals equipped with BESSs (Battery Energy Storage Systems) are simulated. A dynamic model of BESS operation is optimized using a balanced hybrid metaheuristic algorithm combining GA-PSO-BFO (Genetic Algorithm-Particle Swarm Optimization-Bacterial Foraging Optimization). Simulations under 50% and 80% transformer loading conditions assess the effects of charge-only versus charge–discharge strategies. Results indicate that coordinated charge–discharge control improves voltage stability by 1.0–1.5%, reduces transformer loading by 3–4%, and decreases feeder line loading by 2.5–3.5%. Conversely, charge-only coordination offers negligible benefits. Further, quasi-dynamic analyses validate the system’s enhanced stability under coordinated energy management. These findings highlight the potential of docked electric ferries, operating under intelligent control, to act as distributed energy reserves that enhance grid flexibility and operational efficiency. Full article

Diseases caused by infection are a threat to human health and the world economy, with bacterial infections being responsible for a large portion of hospitalizations, morbidity, and mortality, which necessitates the quest for advanced medications and/or sustainable antibacterial strategies. This study aims to develop bioderived chitin nanofibers (ChNFs) and ZnO nanoparticles to produce non-toxic nanohybrid materials with improved aqueous stability and enhanced antibacterial properties. These nanohybrids were formed via either (i) an ex situ route by mixing the ChNFs with ZnO nanoparticles prepared by flame spray pyrolysis or (ii) an in situ route resulting in ZnO nanoparticles being formed and embedded into ChNFs by a simple aqueous hydrothermal process, utilizing a low-cost Zn inorganic precursor. The ChNFs, the ZnO nanoparticles, and the nanohybrids were physicochemically characterized for their size, morphology, charge and stability. Their antibacterial activity was evaluated against Gram (−) E. coli and Gram (+) S. aureus bacteria, while their cytocompatibility was assessed against mammalian cell lines. The obtained results reveal a balance between antibacterial activity and cytocompatibility, as both nanohybrids exhibited satisfactory antibacterial activity (MIC 200–300 μg/mL) combined with low cytotoxicity against mammalian cell lines (cell viability 80–100%), indicating that their further application as safe and effective antibacterial agents is promising. Full article

In this study, polyethersulfone (PES)/sulfonated polyethersulfone (SPES) composite nanofiltration membranes doped with different contents of monolayer titanium carbide nanosheets (Ti₃C₂T_X) were prepared by the nonsolvent induced phase inversion (NIPS) method. The effects of Ti₃C₂T_X on membrane structure, separation performance and antibacterial activity were investigated systematically. The results demonstrated that the viscosity of the casting solution increased significantly with the increasing content of Ti₃C₂T_X. In addition, the pore size of the membrane surface first decreased and then increased; porosity and hydrophilicity were optimized synchronously; and the density of negative charges on the surface increased. The M2 membrane showed a rejection rate of more than 90% for Metanil yellow (MY) and methylene blue (MEB). The order of salt ion rejection rates was magnesium sulfate (MgSO₄) > sodium sulfate (Na₂SO₄) > sodium chloride (NaCl), and water flux reached the peak (18.5 L/m²·h·bar). The antibacterial activity of the M2 membrane was significantly enhanced, and its antibacterial rate against Bacillus subtilis increased from 15% (M0) to 58%. This phenomenon was attributed to the synergistic mechanism of the Ti₃C₂T_X physical capture effect, reactive oxygen species (ROS) generation and sharp edge damage to bacterial cell membranes. This study provides theoretical support and a technical path for the development of MXene composite membranes with high separation efficiency and excellent antibacterial properties. Full article

Background/Objectives: Extracellular vesicles (EVs) are nanoscale, membrane-enclosed structures that play key roles in intercellular communication and biological regulation. Among them, Lactobacillus paracasei-derived EVs (Lp-EVs) have attracted attention for their anti-inflammatory and anti-aging properties, making them promising candidates for therapeutic and cosmetic use. However, methods for specific detection and quantitative evaluation of Lp-EVs are still limited. This study aims to develop a surface plasmon resonance (SPR)-based sensor system for the precise and selective detection of Lp-EVs. Methods: Anti-p40 antibodies were immobilized on gold thin films to construct an SPR sensing platform. The overexpression of the p40 protein on Lp-EVs was confirmed using flow cytometry and Western blotting. For functional evaluation, Lp-EVs were applied to an artificial skin membrane mounted on a Franz diffusion cell, followed by SPR-based quantification and fluorescence imaging to assess their skin penetration behavior. Results: The developed SPR sensor demonstrated high specificity and a detection limit of 0.12 µg/mL, with a linear response range from 0.1 to 0.375 µg/mL. It successfully discriminated Lp-EVs from other bacterial EVs. In the skin diffusion assay, Lp-EVs accumulated predominantly in the epidermal layer without penetrating into the dermis, likely due to their negative surface charge and interaction with the hydrophobic epidermal lipid matrix. Fluorescence imaging confirmed this epidermal confinement, which increased over 24 h. Conclusions: This study presents a sensitive and selective SPR-based platform for detecting Lp-EVs and demonstrates their potential for targeted epidermal delivery. These findings support the use of Lp-EVs in skin-focused therapeutic and cosmetic applications. Future studies will explore strategies such as microneedle-assisted delivery to enhance transdermal penetration and efficacy. Full article

Campylobacter spp. is one of the most prevalent causes of zoonotic foodborne infections associated with diarrhea in humans. The growing threat of antibiotic resistance calls for innovative approaches. The antimicrobial lipopeptide brevibacillin produced by Brevibacillus laterosporus and its synthetic analog brevibacillin Thr1 showed promising activity against Salmonella and E. coli. The latter is a 1602.13 Da positively charged (+3) synthetic peptide of 13 residues that showed reduced cytotoxicity (IC₅₀ of 32.2 µg/mL against Caco-2 cells) and hemolytic activity (1.2% hemolysis at 128 µg/mL) compared to the native peptide. It contains an N-terminal L-isoleucic fatty acid chain and four non-proteinogenic amino acids and ends with valinol at its C-terminus. One key structural modification is the substitution of α,β-dehydrobutyric acid with threonine. We investigated the antimicrobial potential of the synthetic brevibacillin Thr1 analog against a collection of 44 clinical Campylobacter spp. that were obtained from two reference laboratories. Susceptibility testing revealed marked resistance to ciprofloxacin, tetracycline, and ampicillin among the strains, with more than half expressing a multidrug-resistant phenotype. The genomes of the 44 strains were sequenced to study the genes responsible for their antimicrobial resistance. Tetracycline resistance was associated with tet(O), ciprofloxacin resistance with mutations in gyrA and regulatory sequences modulating the expression of an efflux system, and aminoglycoside resistance with genes of the aph family. The brevibacillin Thr1 analog was produced by chemical synthesis, and evaluation of its activity against a subset of clinical strains by microdilution revealed minimum inhibitory concentration and minimum bactericidal concentration ranging from 8 µg/mL to 64 µg/mL. The peptide was active against multidrug-resistant isolates with a bactericidal effect. Of note, despite numerous attempts, it proved impossible to select Campylobacter spp. for resistance to the brevibacillin Thr1 analog. These results underline the potential of lipopeptides, notably brevibacillin, as antimicrobial alternatives against antibiotic-resistant Campylobacter bacterial infections. Full article

Global water scarcity and antimicrobial resistance (AMR) represent two escalating crises that urgently demand integrated and effective solutions. While wastewater reuse is increasingly promoted as a strategy to alleviate water scarcity, conventional treatment processes often fail to eliminate persistent contaminants and antibiotic-resistant microorganisms. Cold plasma (CP), a non-thermal advanced oxidation process, has demonstrated the strong potential to simultaneously inactivate pathogens and degrade micropollutants. CP generates a diverse mix of reactive oxygen and nitrogen species (ROS and RNS), as well as UV photons and charged particles, capable of breaking down complex contaminants and inducing irreversible damage to microbial cells. Laboratory studies have reported bacterial log reductions ranging from 1 to >8–9 log₁₀, with Gram-negative species such as E. coli and Pseudomonas aeruginosa showing higher susceptibility than Gram-positive bacteria. The inactivation of endospores and mixed-species biofilms has also been achieved under optimized CP conditions. Viral inactivation studies, including MS2 bacteriophage and norovirus surrogates, have demonstrated reductions >99.99%, with exposure times as short as 0.12 s. CP has further shown the capacity to degrade antibiotic residues such as ciprofloxacin and sulfamethoxazole by >90% and to reduce ARGs (e.g., bla, sul, and tet) in hospital wastewater. This perspective critically examines the mechanisms and current applications of CP in wastewater treatment, identifies the operational and scalability challenges, and outlines a research agenda for integrating CP into future water reuse frameworks targeting AMR mitigation and sustainable water management. Full article