Search Results (4,595)

Background/Objectives: In this proof-of-concept study, the objective was to evaluate the phenotypic CarbaLux combination rapid test in terms of guiding the therapy of infections caused by multidrug-resistant Gram-negative bacteria with carbapenemase inhibitors and carbapenems, and to compare its results and practicability with standard diagnostic methods. Methods: In the classical CarbaLux test, a fluorescent carbapenem serves as a UV–visible diagnostic surrogate for clinically used carbapenem antibiotics. When exposed to extracted carbapenemases from bacterial colony growth on agar plates, fluorescence rapidly disappears, showing whether monotherapy with carbapenems is possible or must be rejected. It was expected that a specific inhibitor that protects imipenem or meropenem from enzymatic deactivation during antibacterial therapy would perform the same in vitro with fluorescent carbapenem and preserve its fluorescence. The new additional CarbaLux combination test is used if the classic test is positive for carbapenemases: a classic test tube pre-dosed with fluorescent carbapenem is spiked with cloxacillin; with recently launched carbapenemase inhibitors, e.g., avibactam, relebactam, zidebactam, nacubactam, or vaborbactam; or with picolinic acid. Fourteen Enterobacterales and six Acinetobacter baumannii isolates were analyzed. Results: At fixed concentrations, the new inhibitors protected fluorescent carbapenem from bacterial KPC-mediated inactivation and partially from AmpC beta-lactamase-mediated inactivation. In addition, avibactam also effectively inhibited OXA-48-like enzymes. Cloxacillin selectively inhibited AmpC beta-lactamases extracted from Enterobacter complex species. Non-therapeutic picolinic acid was specific for metallo-beta-lactamases and thus identified infections by pathogens that cannot be treated with carbapenems alone or in combination. Conclusions: Inhibitor/fluorescent carbapenem mixtures corresponding to therapeutic inhibitor/carbapenem combinations allow us to visualize the efficacy of carbapenemase inhibitors. The in vitro results are consistent with clinical experience regarding combination therapy. Enzymatic assays provide a rapid yes/no answer for carbapenem mono- or combination therapy and offer several advantages over current carbapenemase testing methods. In contrast to PCR and lateral flow tests, which only target a selection of carbapenemases, enzymatic assays work by employing a reproducible phenotypic mechanism. They are simpler, broader in scope, and more cost-effective; they can also detect antimicrobial heteroresistance or AmpC beta-lactamase hyperproduction, which is normally undetected when performing automated antibiotic susceptibility testing. The new tests are suitable for clinical diagnosis, public health purposes, and infection control. Full article

Historically, clays have been widely used for the treatment of wounds and to stop hemorrhaging. The aim of this study was to combine four natural clay minerals (kaolinite, glauconite, montmorillonite, and bentonite) with magnetite (Fe₃O₄) nanoparticles to produce Fe₃O₄–clay complexes with enhanced antimicrobial properties and chemopreventive activity against melanoma. The magnetite–clay complexes were synthesized by the chemical co-precipitation method and characterized using XRD, TEM, STEM-EDS, SEM, and SQUID magnetometer. Antimicrobial properties were determined by evaluation of MIC values. The most promising materials were also subjected to direct contact antibacterial test according to the OECD standard for porous materials. Cytotoxicity of the complexes towards melanoma cells and normal human skin fibroblasts was assessed by MTT assay. We performed XRD, which confirmed the formation of Fe₃O₄–clay complex materials. It was also proven that complexes exhibited superparamagnetic properties. Microbiological experiments clearly revealed that modification of natural clays with magnetite significantly boosted their antimicrobial properties. Fe₃O₄–montmorillonite and Fe₃O₄–bentonite showed the strongest antimicrobial activity. Moreover, the mentioned complexes had the ability to reduce the viability of melanoma cells by 35–40%, while exhibiting no cytotoxicity against the normal human fibroblast (BJ) cell line, which is an extremely desirable feature. Thus, it may be concluded that Fe₃O₄–montmorillonite and Fe₃O₄–bentonite complexes hold promise for use in the management of infected wounds and wounds after melanoma excision. Full article

Background/Objectives: In recent years, silver complexes have shown strong antibacterial, antifungal, and antitumor activity with high selectivity toward cancer cells. Their cytotoxic effects are mainly linked to apoptosis induction, DNA damage, and enzyme inhibition, while the antitumor activity of silver(I) complexes with S-alkyl thiosalicylic acid derivatives remains unexplored. Methods: Silver(I) complexes with S-alkyl derivatives of thiosalicylic acid (C1–C5) were obtained through the direct reaction of silver(I) nitrate, the corresponding ligand of thiosalicylic acid, and a sodium hydroxide solution. The interactions between the complexes and CT-DNA/BSA were studied using UV-Vis, fluorescence spectroscopy, and molecular docking studies. The cytotoxic capacity of the newly synthesized complexes was assessed by an MTT assay. Results: Complexes C1–C5 exhibited strong cytotoxicity against murine and human breast (4T1, MDA-MB-468), colon (CT26, HCT116), and lung (LLC1, A549) cancer cell lines. The C3 complex significantly diminished tumor progression in an orthotropic mammary carcinoma model while demonstrating good systemic tolerance. Conclusions: The tested complex C3 triggered apoptosis in 4T1 cells by altering the delicate balance between pro- and anti-apoptotic Bcl-2 family members, increasing reactive oxygen species (ROS) levels, and reducing mitochondrial membrane depolarization. Moreover, the C3 arrested the 4T1 cell cycle in G0/G1 phase, decreasing the expression of cyclin D3 and increasing the expression of p16, p21, and p27. Full article

In the pursuit of addressing the persistent challenge of bacterial adhesion and biofilm formation in dental care, this study investigates the efficacy of electric current as an alternative strategy, specifically focusing on its application in dental contexts. Polyether ether ketone (PEEK), known for its excellent biocompatibility and resistance to bacterial plaque, was enhanced with conductive properties by incorporating silver (Ag), a well-known antibacterial material. Through systematic in vitro experiments, the effectiveness of alternating current (AC) and direct current (DC) in reducing bacterial proliferation was evaluated. The tests were conducted using two bacterial strains: the Gram-positive Staphylococcus aureus and the Gram-negative Pseudomonas aeruginosa. Various configurations, current parameters, and two different electrode configurations were assessed to determine their impact on bacterial reduction. A notable finding from this study is that alternating current (AC) demonstrates superior efficacy compared to direct current (DC). The more significant decrease in CFUs/mL for P. aeruginosa with AC was recorded at the current levels of 5 mA and 500 nA. In opposition, S. aureus exhibited the greatest reduction at 5 mA and 1 mA. This study highlights the potential of using electric current within specific intensity ranges as an alternative strategy to effectively mitigate bacterial challenges in dental care. Full article

We report for the first time a method for forming polyacrylate nanoparticles using N-acryloylciprofloxacin as a sole monomer for emulsion polymerization. The procedure involves a free radical-induced emulsion polymerization of N-acryloylciprofloxacin monomer to produce a stable aqueous emulsion comprising uniformly sized polyacrylate nanoparticles. Dynamic light scattering analysis of the emulsions showed a single population of nanoparticles having an average diameter of 970 nm and average surface charge of −63 mV, indicative of the high stability of the emulsion and significantly enhance lipophilicity of the polymeric matrix of the nanoparticle. Antibacterial testing of the emulsions against the Gram-positive microbe Staphylococcus aureus and the Gram-negative Escherichia coli found in vitro activities identical to those of the reference clinical agent, ciprofloxacin. Assays against human colorectal carcinoma cells and human embryonic kidney cells showed essentially no cytotoxicity. This is the first study on the synthesis of aqueous nanoparticle emulsions assembled solely from a single monomer derived from the antibiotic agent. Full article

Early-life rearing of animals is critical for their lifelong productivity, health, and the quality/safety of livestock products. EHE, a feed additive with growth-promoting, antibacterial, and immunity-enhancing properties, was tested for effects on preweaned calves. Forty-eight calves (42.18 ± 0.61 kg) were randomly assigned to four groups (n = 12/group), fed milk replacer with 0 (CON), 400 (A), 800 (B), or 1200 (C) mg/d EHE for 60 d (after 6 d adaptation). Growth, nutrient digestibility, serum biomarkers, rumen fermentation, and diarrhea incidence were measured; network pharmacology was used to analyze EHE’s targets. Results: Group C had 14.09% higher body weight gain (52 vs. 45 kg, p < 0.05), higher dry matter intake/digestibility, and increased acid detergent fiber digestibility vs. CON. Group C had reduced diarrhea frequency, tended to have lower rumen acetate-to-propionate ratio, and had higher early rumen volatile fatty acids (VFA). At d 66, Groups B and C had reduced serum IL-6/IL-8 (p < 0.05). Network pharmacology identified 256 anti-inflammatory targets (e.g., BCL2, IL6) involved in apoptosis/inflammatory pathways. Conclusion: 1200 mg/d EHE optimally improves calf growth, digestibility, and anti-inflammatory status. Full article

Mycobacterium avium complex (MAC) infections present significant therapeutic challenges due to their inherent antibiotic resistance, demanding innovative treatment approaches. This study investigated the antimicrobial and antioxidant potential of a novel compound, Fullerene Gallium Phosphonate (FGP), and compared its effects against a previously tested similar compound, Fullerene Disodium Phosphonate (FDSP). Results of experiments using MAC cultures and infected THP-1 macrophages treated with varying FGP and FDSP concentrations (1, 10, 100 µg/mL) revealed that FGP demonstrated greater efficacy than FDSP in reducing M. avium colony-forming units (CFU), achieving a nearly 3-fold reduction by day 8, compared to a 2-fold decrease with FDSP. In infected macrophages, FGP significantly decreased bacterial load at 1 and 10 µg/mL (p < 0.01). FGP also lowered oxidative stress, reflected by a significant reduction in malondialdehyde (MDA) levels on day 4 (p < 0.05) and decreased IL-6 (2-fold) and TNF-α levels (3-fold) by day 8, indicating both antimicrobial and anti-inflammatory effects. However, FGP paradoxically increased MAC burden at its highest concentration and showed no significant difference in efficacy of different concentrations. These findings suggest that FGP may serve as a promising candidate for antimycobacterial therapy with dual antibacterial and antioxidant effects. Further research is crucial to fully elucidate its mechanism of action and find the optimal therapeutic window. Full article

Antimicrobial peptides are potential alternatives to conventional antibiotics, primarily due to broad-spectrum activity and low propensity for inducing bacterial resistance. However, their clinical translation faces challenges, including peptide stability and potential mammalian cell toxicity. This study centers on DGL13K, an all D-amino acid peptide, which overcomes proteolytic susceptibility and demonstrates notable stability and broad-spectrum bactericidal activity without inducing de novo bacterial resistance. This work aimed to enhance the therapeutic properties of DGL13K by using targeted modifications to increase antimicrobial potency and decrease toxicity, as determined by hemolysis. DGL13K derivatives were synthesized and tested, involving amino acid substitutions, stereochemical alterations, and N-terminal functionalization with polyethylene glycol (PEG) or myristoylate. While some modifications altered bacterial specificity and reduced hemolytic activity, none of the tested alterations resulted in a substantial overall improvement compared to the parent DGL13K sequence. Furthermore, the antibacterial efficacy of DGL13K and its variants was significantly inhibited in the presence of 50% serum, suggesting limitations for systemic applications. The findings suggest that the DGL13K sequence, derived from an evolutionarily selected protein, is already highly optimized. Given its stability, broad-spectrum efficacy, in vivo activity, low resistance profile, and high safety margin, DGL13K is a promising therapeutic candidate for topical/localized infections. Full article

Edible and medicinal plants provide a treasure trove of natural phytochemicals for mining the next generation of green food preservatives. Herein, we evaluated antibacterial activities of 55–95% ethanol extracts from the edible rhizome of Rumex madaio (RmEEs). The 75% ethanol extract displayed the strongest antibacterial activity, and its purified fraction 2 (RmEE-F2) blocked the proliferation of common pathogens Staphylococcus aureus and Vibrio cholerae, with minimum inhibitory concentrations (MICs) of 391 μg/mL. RmEE-F2 (1 × MIC) altered the bacterial cell surface biophysical parameters and impaired cell structure, resulting in intracellular nucleic acid and protein leakage. It manifested bacteriostatic rates of 88.21–91.17% against S. aureus and V. cholerae in spiked fish (Carassius auratus) and shrimp (Penaeus vannamei) during storage at 4 °C for 24 h. Meanwhile, RmEE-F2 effectively rendered the pH rising and reduced lipid oxidation and protein degradation of C. auratus and P. vannamei meat samples at 4 °C for 6 days. Additionally, RmEE-F2 (< 781 µg/mL) showed non-cytotoxicity to human colon Caco-2, liver HepG-2, and lung A549 cell lines, and rescued V. cholerae and S. aureus-infected Caco-2 cellcells with enhanced viability of 14.31–16.60% (1 × MIC). Comparative transcriptomic analysis revealed down-regulated protein synthesis, cell wall and cell membrane synthesis, and or DNA replication and repair in the tested bacteria triggered by RmEE-F2. The major antibacterial compounds in RmEE-F2 included melibiose (9.86%), 3-(N, N-dimethylaminomethyl) indole (7.12%), and citric acid (6.07%). Overall, this study underscores the promising potential of RmEE-F2 for aquatic product green preservation. Full article

The escalating crisis of bacterial antimicrobial resistance poses a severe threat to global health, necessitating novel strategies beyond conventional antibiotics. Photothermal therapy (PTT) has emerged as a promising alternative that leverages heat generated by laser irradiation to induce localized cellular damage and eradicate bacteria. Among various photothermal agents, carbon-based nanomaterials like graphene nanoplatelets (GNPs) offer exceptional properties for PTT applications. This study introduces a novel urinary catheter (UC) embedded with GNPs (GNPUC), specifically designed for photothermal sterilization to combat catheter-associated bacterial infections. GNPs were systematically incorporated into polydimethylsiloxane (PDMS) catheters at varying weight percentages (1% to 10%). The fabricated GNPUCs exhibited low wettability, hydrophobic characteristics, and low adhesiveness, properties that are crucial for minimizing bacterial interactions and initial adhesion. Upon exposure to near-infrared (NIR) laser irradiation (808 nm, 1.5 W/cm²), the UC containing 10 weight percent of GNPs (10GNPUC) achieved a significant temperature of 68.8 °C, demonstrating its potent photothermal conversion capability. Quantitative agar plate tests confirmed the enhanced, concentration-dependent photothermal antibacterial activity of GNPUCs against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Notably, 5% and higher GNP concentrations achieved 100% mortality of S. aureus, while 1% and higher concentrations achieved 100% mortality of E. coli. These findings underscore the significant potential of GNP-embedded catheters as a highly effective photothermal antibacterial platform for future clinical applications in combating catheter-associated infections. Full article

The rise in the number of cancer cases and the dissemination of strains with multiple drug resistance in the world pose a serious threat to public health care and human well-being. The design and study of new chemotherapeutic agents for cancer and infectious diseases are hot topics in science. Hydrazones, a versatile and diverse class of chemical compounds, gained a lot of attention as a promising base for future drugs. In this paper, we report on the synthesis of eight new gold(III) complexes with hydrazones derived from pyridoxal-5′-phosphate and pyridoxal. The complexes are thoroughly characterized using IR, ¹H, ³¹P NMR, and mass spectroscopy. The cytotoxic effect of twelve various hydrazones derived from pyridoxal 5′-phosphate on both immortalized (HEK293T) and tumor (HCT116) human cell lines was estimated using the MTT assay. In addition, this contribution describes the antibacterial action of complexes of gold(III) and pyridoxal and pyridoxal 5′-phosphate-derived hydrazones, as well as the mixtures of the solutions containing tetrachloroaurate(III) and hydrazones, using the zone of inhibition test. Gold(III) complexes exhibit moderate antibacterial activity against both Gram-positive and Gram-negative bacteria, while free hydrazones show low cytotoxicity and thus could be considered relatively safe for humans. Full article

The present study aimed to evaluate the antifouling efficacy of Piper betle leaf extracts as a bioactive additive for eco-friendly antifouling coatings. The composition of P. betle extract was determined and analyzed. Phytochemical analysis revealed that the ethanol extract of P. betle contained phenolics, tannins, proteins, carbohydrates, and flavonoids, with total phenolic content reaching 260.3 mg GAE/g dry weight and flavonoid content reaching 52.56 mg QE/g dry weight. The antibacterial test results showed that the ethanol extract of P. betle exhibited maximum antibacterial efficacy against E. coli, B. subtilis, S. aureus, and marine bacteria, with inhibition zone diameters of 28.7 ± 0.5, 27.0 ± 1.6, 22.1 ± 0.6, and 35.1 ± 0.5 mm, respectively. Based on the laboratory test results, the ethanol extract of P. betle was chosen to be added to coatings as an antifouling additive. The content of the extract was 0.5, 1.0, and 1.5 wt.%. A field test conducted in tropical seawater (at Nha Trang Bay) demonstrated that incorporating 1 wt.% of P. betle extract into an acrylic copolymer-based coating significantly enhanced its antifouling performance. After nine months of immersion in seawater, this sample maintained an antifouling efficiency of 74%. These findings highlight the potential of P. betle extract as a sustainable alternative to conventional antifouling agents in marine coatings. Full article

Periodontitis is a chronic oral inflammatory disease whose treatment is often hindered by poor drug retention, prolonged therapeutic regimens, and the rise of antibiotic resistance. In this study, we developed a Hydrogel@ZIF-8@metronidazole (Hydrogel@ZIF-8@MNZ) nanocomposite dressing for targeted, sustained, and in situ antimicrobial therapy. This system integrates ZIF-8, a pH-responsive metal–organic framework, with the antimicrobial agent metronidazole (MNZ), encapsulated within a crosslinked hydrogel matrix to enhance stability and retention in the oral environment. Drug release studies demonstrated that MNZ release was significantly accelerated under acidic conditions (pH 5.0), mimicking the periodontal microenvironment. The Hydrogel@ZIF-8 composite achieved a maximum MNZ adsorption capacity of 132.45 mg·g⁻¹, with a spontaneous and exothermic uptake process best described by a pseudo-second-order kinetic model, suggesting chemisorption as the dominant mechanism. The nanoplatform exhibited strong pH-responsive behavior, with enhanced drug release under acidic conditions and potent dose-dependent bactericidal activity against Fusobacterium nucleatum (Fn). At the highest tested concentration, bacterial survival was reduced to approximately 30%, with extensive membrane disruption observed through live/dead fluorescence microscopy. In summary, the stimuli-responsive Hydrogel@ZIF-8@MNZ nanocomposite offers an intelligent and effective therapeutic strategy for periodontitis. By tailoring its action to the disease microenvironment, this platform enables sustained and localized antibacterial therapy, addressing major challenges in the treatment of chronic oral infections. Full article

Background/Objectives: Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human stomach and causes various gastrointestinal diseases. Although antibiotic therapy is the most effective method for its eradication, the increasing prevalence of antibiotic resistance has made treatment increasingly challenging in recent years. In this study, the antimicrobial activity, synergistic effects with antibiotics, and mechanisms of action of Bicarinalin, an antimicrobial peptide (AMP) derived from the venom of Tetramorium bicarinatum, were investigated against H. pylori. Methods: To determine the antibacterial activity of Bicarinalin, a well diffusion assay was performed, yielding an inhibition zone of 18.3 mm at a concentration of 32 µg/mL for ATCC strain. MIC₉₉ values were determined by microdilution tests as 4.8 μg/mL for the reference strain. The enhancement of the antimicrobial potential of levofloxacin and clarithromycin when administered together with Bicarinalin has been demonstrated using the well diffusion method. Results: Inhibition zones increased from 14.2 mm to 20 mm for levofloxacin and from 7.3 mm to 16 mm for clarithromycin. This study is the first to identify DNA and protein leakage caused by Bicarinalin in H. pylori. Intracellular protein and DNA leakage were measured, with protein and DNA levels released into the extracellular environment determined as 33.25% and 55.10%, respectively, following Bicarinalin treatment. Furthermore, to investigate its effect on membrane damage, scanning electron microscopy (SEM) was performed, revealing disrupted cell membrane structures, penetration between cells, and severe deterioration of morphological integrity. Conclusions: This study has demonstrated for the first time that, when administered concomitantly, Bicarinalin enhances the antimicrobial activities of levofloxacin and clarithromycin. This highlights its potential as an adjunctive treatment for H. pylori alongside existing drugs. Full article

Recently, the search for new antimicrobial compounds, including the secondary metabolites of basidiomycetes, has become increasingly important. Representatives of this division of higher fungi have high biosynthetic abilities, which contributes to their use as producers. In this work, extracts of culture liquids and submerged mycelia from 18 strains representing three different orders of basidiomycetes were studied. For this purpose, the submerged cultivation of strains, extraction of biological material, and evaluation of the extract’s antimicrobial activity using the agar well diffusion method were carried out. The minimum inhibitory concentration was determined for extracts with strong activity. The most promising ones were analyzed using HPLC-MS. As a result, it was found that 16 strains contained antimicrobial metabolites. Thus, the strains selected for further work were Hericium corraloides 4, which showed not only the antibacterial but also antifungal activity of cultural liquid and submerged mycelia extracts, and Fomitopsis betulina 3, Fomitopsis pinicola 2, Hericium erinaceus 1, and Laetiporus sulphureus 4, whose cultural liquid extracts exhibited high antibacterial activity against Gram-positive and Gram-negative test cultures. For these strains, metabolic profiles were obtained using the method HPLC-MS. Using this method, two metabolites were preliminary identified: hericerin in H. erinaceus 1 and sulfureuine H in L. sulphureus 4. Full article