Antibacterial Activity Research Articles

Synthesis of new 1,4-dihydropyridine derivative, anti-cancer, bacterial activity, molecular docking and adsorption, distribution, metabolism and excretion analysis.

Aim: The amination and cyclization method developed a new strategy for designing and assembling new 1,4-dihydropyridine derivatives of compounds 3a-g and 4a-g.Methods & materials: Newly prepared pyridine compounds are more economical, and reduce the reaction time. FT-IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analyses elucidated the synthesized derivatives. All the derivatives are subjected to in vitro assay against MCF-7 (breast) and anti-bacterial activity.Results: In the anti-bacterial activity compound 3c is moderately active against Escherichia coli (6.0g/ml), and 4c is extremely active against Lactiplantibacillus plantarum (10.0g/ml) compared with standard Erythromycin. In cytotoxic activity, the compound 3g (lC50 24.5μM) is slightly active against standard doxorubicin. We also present the outcome of a molecular docking study connecting the methoxsalen (Protein Data Bank, PDB ID: 1Z11). Compound 3g shows a higher binding affinity (-7.7Kcal/mol) matching up with doxorubicin(-9.0Kcal/mol). The synthesized analogs were predicted for their adsorption, distribution, metabolism and excretion profiles and pharmacokinetics. The compound 3g has three rotatable bonds (NROB≤10), five hydrogen bond acceptors (HBA≤10) and four hydrogen bond donors (HBD≤5). All the compounds follow Lipinski's rule.Conclusion: Therefore, the compounds 3c and 3g are used as cytotoxic and anti-bacterial drugs in feature.

Colistin-niclosamide-loaded nanoemulsions and nanoemulsion gels for effective therapy of colistin-resistant Salmonella infections.

Colistin (COL) is regarded as a last-resort treatment for infections by multidrug-resistant (MDR) Gram-negative bacteria. The emergence of colistin-resistant Enterobacterales poses a significant global public health concern. Our study discovered that niclosamide (NIC) reverses COL resistance in Salmonella via a checkerboard assay. However, poor solubility and bioavailability of NIC pose challenges. In this study, we prepared a self-nanoemulsifying drug delivery system (SNEDDS) co-encapsulating NIC and COL. We characterized the physicochemical properties of the resulting colistin-niclosamide-loaded nanoemulsions (COL/NIC-NEs) and colistin-niclosamide-loaded nanoemulsion gels (COL/NIC-NEGs), assessing their antibacterial efficacy in vitro and in vivo. The COL/NIC-NEs exhibited a droplet size of 19.86 nm with a zeta potential of -1.25 mV. COL/NIC-NEs have excellent stability, significantly enhancing the solubility of NIC while also demonstrating a pronounced sustained-release effect. Antimicrobial assays revealed that the MIC of COL in COL/NIC-NEs was reduced by 16-128 times compared to free COL. Killing kinetics and scanning electron microscopy confirmed enhanced antibacterial activity. Antibacterial mechanism studies reveal that the COL/NIC-NEs and COL/NIC-NEGs could enhance the bactericidal activity by damaging cell membranes, disrupting proton motive force (PMF), inhibiting multidrug efflux pump, and promoting oxidative damage. The therapeutic efficacy of the COL/NIC-NEs and COL/NIC-NEGs is further demonstrated in mouse intraperitoneal infection models with COL-resistant Salmonella. To sum up, COL/NIC-NEs and COL/NIC-NEGs are a potentially effective strategies promising against COL-resistant Salmonella infections.

Electrospun Cellulose Acetate/Poly(Vinyl Alcohol) Nanofibers Loaded with Methyl Gallate and Gallic Acid for Anti-Staphylococcus aureus Applications

Methyl gallate (MG) and gallic acid (GA) are natural compounds with potent activity against methicillin-resistant Staphylococcus aureus (MRSA), a significant global health concern. In this study, MG and GA were incorporated into cellulose acetate (CA) blended with poly(vinyl alcohol) (PVA) to create electrospun nanofibers aimed at combating both methicillin-susceptible S. aureus (MSSA) and MRSA. Key electrospinning parameters—DC voltage, injection flow rate, and syringe tip–collector distance—were optimized, with the best conditions being a 1.5 mL/h flow rate, 30 cm distance, and 20 kV voltage. The resulting nanofiber mats were characterized by SEM, FTIR, DSC, tensile strength testing, contact angle measurement, swelling behavior, and release profiling. Antibacterial properties were assessed using the agar diffusion test. The obtained nanofibers had diameters ranging from 879.33 to 906.13 nm. Among the samples, MG-GA-CA/PVA exhibited the highest tensile strength, good flexibility, and improved stiffness, which was related to enhanced thermal stability and chemical interactions as shown by DSC and FTIR analyses. This formulation also displayed excellent hydrophilicity, swelling properties, and a consistent release profile over 8 to 24 h. Furthermore, MG-GA-CA/PVA showed superior antibacterial activity against both MSSA and MRSA, suggesting its potential as a strong, flexible, and effective anti-S. aureus material.

Plukenetia volubilis leaves as source of anti-Helicobacter pylori agents.

Helicobacter pylori infection is a major issue worldwide, with widespread prevalence, combined with its link to gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Meanwhile, effectiveness of current treatment protocols is limited by increasing antibiotic resistance and patient compliance issues due to long regimens and side effects. Plukenetia volubilis, or sacha inchi, is a valuable source of bioactive molecules. However, studies on its antimicrobial activity, especially against H. pylori, are lacking. In this study, the anti-H. pylori activity of P. volubilis leaves water extract was explored using in vitro and in silico approaches. High-Performance Liquid Chromatography coupled to Electrospray Ionisation and Quadrupole Time-of-Flight Mass Spectrometry (HPLC-ESI- QTOF-MS-MS) analysis of the water extract from the leaves was used to characterise the chemical composition of the plant and allowed identification of some flavonoids, such as astragalin, and some phenolic compounds. Then, high-speed counter current chromatography (HSCCC) was used to fractionate the ethyl acetate partition obtained from the water extract from the leaves. The presence of flavonoids derived from kaempferol was confirmed and astragalin was isolated for the first time in P. volubilis. The P. volubilis water infusion, ethyl acetate extract and the isolated astragalin exhibited anti-bacterial activity against H. pylori J99 and two clinical isolates (e.g., minimum inhibitory concentrations of 0.53, 0.51 and 0.49μg/mL, respectively, for clarithromycin-resistant clinical isolate SSR366). Then, using molecular docking for potential protein targets for H. pylori, it was verified that astragalin could interact with these proteins by in silico analysis. These findings highlight that P. volubilis and astragalin produce a bacteriostatic activity against H. pylori and may have potential to be used in treatment against H. pylori, after further research.

Antibacterial activity of green synthesized copper oxide nanoparticles against multidrug-resistant bacteria

Using plant extracts in the green synthesis of nanoparticles has become an environmentally acceptable approach. In our study, copper oxide nanoparticles (CuO NPs) were synthesized using ethanolic extracts of Azadirachta indica and Simmondsia chinensis. CuO NP formation was confirmed by the change in color and by UV‒visible spectroscopy (CuO NPs peaked at a wavelength of 344 nm). TEM images confirmed the semispherical shape of the CuO NPs, with particle sizes ranging from 30.9 to 10.7 nm. The antibacterial activity of these NPs was evaluated by using the agar diffusion method against clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Pseudomonas aeruginosa, Acinetobacter spp., Klebsiella pneumoniae, and Stenotrophomonas maltophilia. The minimum inhibitory concentration (MIC) of CuO NPs ranged from 62.5 to 125 µg/ml. In contrast, the antioxidant activity and antibiofilm activity of CuO NPs ranged from 31.1 to 92.2% at 125–500 µg/ml and 62.2–95%, respectively, at 125 –62.5 µg/ml. Our results confirmed that CuO NPs had IC50s of 383.41 ± 3.4 and 402.73 ± 1.86 at 250 µg/mL against the HBF4 cell line. Molecular docking studies with CuO NPs suggested that penicillin-binding protein 4 (PBP4) and beta-lactamase proteins (OXA-48) strongly bind to S. aureus and K. pneumoniae, respectively, with CuO NPs. Our study confirms the promising use of CuO NPs in treating pathogenic bacteria and that CuO NPs could be possible alternative antibiotics. This study supports the pharmaceutical and healthcare sectors in Egypt and worldwide.

A novel broad-spectrum antibacterial and anti-malarial Anopheles gambiae Cecropin promotes microbial clearance during pupation.

Anophelinae mosquitoes are exposed to a variety of microbes including Plasmodium parasites that cause malaria. When infected, mosquitoes mount versatile immune responses, including the production of antimicrobial peptides. Cecropins are one of the most widely distributed families of antimicrobial peptides in insects and all previously studied Anopheles members are playing roles in adult mosquito immunity. We have identified and characterized a novel member of the Anopheles gambiae cecropin family, cecropin D (CecD), that is uniquely expressed and immune-responsive at late larval stages to promote microbial clearance through its broad-spectrum antibacterial activity during larval-pupal developmental transition. Interestingly, Cecropin D also exhibited highly potent activity against Plasmodium falciparum sporozoites, the malaria parasite stage that is transmitted from mosquitoes and infects humans and thereby holds promise as a malaria transmission-blocking agent. Finally, we have defined unequivocal cecropin-specific molecular signatures to systematically organize the diversity of the cecropin family in malaria vectors.

Inappropriate ceftriaxone utilization and predictor factors in Ethiopia: a systematic review and meta-analysis

Ceftriaxone stands as a cornerstone in global antibiotic therapy owing to its potent antibacterial activity, broad spectrum coverage, and low toxicity. Nevertheless, its efficacy is impeded by widespread inappropriate prescribing and utilization practices, significantly contributing to bacterial resistance. The aim of this study is to determine the overall national pooled prevalence of inappropriate ceftriaxone utilization and its predictor factors in Ethiopia. A systematic search was conducted across multiple databases including, PubMed, Science Direct, Hinari, Global Index Medicus, Scopus, Embase, and a search engine, Google Scholar, to identify relevant literatures that meet the research question, from March 20 to 30, 2024. This meta-analysis, which was conducted in Ethiopia by incorporating 17 full-text articles, unveiled a national pooled inappropriate ceftriaxone utilization of 55.24% (95% CI, 42.17%, 68.30%) with a substantial heterogeneity index (I2 = 99.24%, p value < 0.001). The review has also identified predictive factors for the inappropriate use of ceftriaxone: empiric therapy (AOR 21.43, 95% CI; 9.26–49.59); multiple medication co-prescription (AOR: 4.12, 95% CI; 1.62–8.05). Emergency ward (AOR: 4.22, 95% CI; 1.8-12.24), surgery ward (AOR: 2.6, 95% CI; 1.44–7.82) compared to medical ward, prophylactic use (AOR: 500, 95% CI; 41.7–1000), longer hospital stay-8-14 Days; (AOR: 0.167, 95% CI; 0.09–0.29), > 14 days; (AOR: 0.18, 95% CI; 0.1–0.32). The study reveals a high national pooled prevalence of inappropriate ceftriaxone utilization, standing at 55.24%, highlighting a significant hazard in the use of this antibiotic. This could be attributed to instances of overuse, misuse or prescription practices that deviates from established guidelines. This eminent challenge can lead to the development of antibiotic resistance, increased healthcare costs, adverse drug reactions, and treatment failures, necessitating multifaceted approach such as improved antibiotic stewardship, better adherence to guidelines, and enhanced clinician education on appropriate antibiotic use.

Heterometallic [2]Catenane-Crosslinked Supramolecular Networks with Improved Antibacterial Activity.

The construction of supramolecular networks with novel crosslinks is of great significance in expanding their chemical structures and exploring their advanced functions. Herein, we prepare a type of [2]catenane-cored supramolecular networks based on the crosslinking of polyethylene glycol (PEG) using a heterometallic [2]catenane unit. By adjusting the molecular weight of PEG, the solubility of the networks can be tuned and gels are formed using low molecular weight PEG. The introduction of heterometallic [2]catenane offers the networks good antibacterial properties owing to the synergistic antimicrobial activity of Pt(II) and Cu(I) ions in the [2]catenane. This study provides a simple and efficient strategy for constructing supramolecular networks with topological crosslinks as antibacterial materials, which will promote the structural design and biological applications of supramolecular networks.

A brief review on Antibacterial activity of Citrullus Colocynthis

Due to contamination or the rapid microbial growth that happens naturally in fish, seafood is very poorly preserved. Fish storage facilities commonly employ artificial preservatives to guarantee quality and safety while prolonging shelf life. Natural preservatives originating from plants, animals, and microbes have been shown to have the ability to take the place of synthetic antimicrobials. The bitter fruit Citrullus colocynthis has been used as a natural preservative. It belongs to the family Cucurbitaceae. The wild melon species also known as colocynth produces cantaloupe-sized fruits with a bitter flavor and seeds that are high in protein and oil. It is a prolonged perennial that thrives in xerophilic environments on sandy shores. When young, fruits are plump and speckled with dark green; when ripe, they typically become yellow. Since ancient times, the fruit of colocynthis has been used medicinally. The current study intends to investigate antibacterial properties of C. colocynthis on gram-negative bacteria E.coli &amp; gram positive bacteria S.aureus. Natural antimicrobials derived from plants, animals, and microbes have the potential to replace chemical antimicrobials. Utilizing UV spectrometery, the chemical characterization of extracts was accomplished. Nile tilapia fish species was used for this experiment to determine antibacterial potential of C. colocynthis.

Role of hypothetical protein PA1-LRP in antibacterial activity of endolysin from a new Pantoea phage PA1.

Pantoea ananatis has emerged as a significant plant pathogen affecting various crops worldwide, causing substantial economic losses. Bacteriophages and their endolysins offer promising alternatives for controlling bacterial infections, addressing the growing concerns of antibiotic resistance. This study isolated and characterized the Pantoea phage PA1 and investigated the role of PA1-LRP in directly damaging bacteria and assisting endolysin PA1-Lys in cell lysis, comparing its effect to exogenous transmembrane domains following the identification and analysis of the PA1-Lys and the PA1-LRP based on whole genome analysis of phage PA1. Additionally, this study also explored how hydrophobic region of PA1-LRP (HPP) contributes to bacterial killing when combined with PA1-Lys and examined the stability and lytic spectrum of PA1-Lys under various conditions. Phage PA1 belonging to the Chaseviridae family exhibited a broad host range against P. ananatis strains, with a latent period of 40 minutes and a burst size of 17.17 phages per infected cell. PA1-Lys remained stable at pH 6-10 and temperatures of 20-50°C and showed lytic activity against various Gram-negative bacteria, while PA1-Lys alone could not directly lyse bacteria, its lytic activity was enhanced in the presence of EDTA. Surprisingly, PA1-LRP inhibited bacterial growth when expressed alone. After 24 h of incubation, the OD600 value of pET28a-LRP decreased by 0.164 compared to pET28a. Furthermore, the lytic effect of co-expressed PA1-LRP and PA1-Lys was significantly stronger than each separately. After 24 h of incubation, compared to pET28a-LRP, the OD600 value of pET28a-Lys-LRP decreased by 0.444, while the OD420 value increased by 3.121. Live/dead cell staining, and flow cytometry experiments showed that the fusion expression of PA1-LRP and PA1-Lys resulted in 41.29% cell death, with bacterial morphology changing from rod-shaped to filamentous. Notably, PA1-LRP provided stronger support for endolysin-mediated cell lysis than exogenous transmembrane domains. Additionally, our results demonstrated that the HPP fused with PA1-Lys, led to 40.60% cell death, with bacteria changing from rod-shaped to spherical and exhibiting vacuolation. Taken together, this study provides insights into the lysis mechanisms of Pantoea phages and identifies a novel lysis-related protein, PA1-LRP, which could have potential applications in phage therapy and bacterial disease control.

New nano-chemotherapeutic chitosans- garlic oil - antibiotics against diabetic foot virulent Proteus spp

Background and Objectives: Diabetes foot ulcer is recognized to have a major side effect that raises the risk of amputation. Diabetic ulcer bacterial infections caused by virulent and resistant bacteria like Proteus mirabilis lead to serious wounds that are incurable with conventional medications. Materials and Methods: In this study, we evaluated the antibacterial activity of a natural product nanochitosan - garlic oil against ten diabetic foot isolates of Proteus mirabilis. Various chitosans (Crab (CScr) - shrimp (CSsh) - squilla (CSsq)) in nano form were prepared and coated with garlic oil (GO). GC-MS analysis was carried out to determine the main compo- nents of the essential garlic oil. The physicochemical properties of GO-NCSsq were analyzed using dynamic light scattering (DLS), zeta potentials (ZP) and subsequently scan electron microscope (SEM). Additionally, the minimum inhibitory con- centration (MIC) and fraction inhibitory concentration index (FICI) were determined. Results: GC-MS analysis revealed the presence of major palmitic fatty acid. (GO) loaded on nanochitosan squilla (NCSsq) showed high activity. Although SEM showed lower nano-size, average size of the GO-NCSsq was 330.8 nm by DLS and its zeta potential formulation was +39.6 mV. The final formulation represented by GO-NCSsq + Pipercillin (Pi) inhibited the virulence factor of P. mirabilis and reduced the MIC value (p-value &gt; 0.001). Moreover, the killing time at 9 h was found to be significantly higher for GO-NCSsq + pipercillin (Pi) against P. mirabilis. Conclusion: In order to manage diabetic foot infections, GO-NCSsq is a legitimate antibacterial agent that can be coupled with other antibiotics.

The effect of a probiotic drug on an enterosorbent on the change in the functional activity of humoral factors of nonspecific immunity of the Russian Lena sturgeon (Acipenser gueldenstadtii × Acipenser baeri)

In modern aquaculture, probiotic drugs are used to increase the immunologically determined natural resistance of the fish body, regulate their immune homeostasis, prevent stress, prevent diseases and form normal intestinal microflora of fish at all stages of development. The use of these drugs in compound feeds can solve a number of problems related to the immunological and physiological state of the fish body, affecting the antimicrobial activity expressed by the secretion of antimicrobial peptides, suppression of bacterial invasion, and prevention of adhesion of pathogenic microorganisms to epithelial cells. In addition, the drugs will help to improve the barrier function, expressed by an increase in mucus production, strengthening the integrity of the epithelial barrier. This article presents information about the experimental study of the effect of a probiotic drug on the enterosorbent “Ecoflor” on the dynamics of bactericidal activity of blood serum, the concentration of nonspecific immune complexes in blood serum and immunocompetent organs, the number of immunodeficient individuals, as well as on the level of C-reactive protein of the Russian Lena sturgeon (Acipenser gueldenstadtii x Acipenser baeri). It was found that the use of a probiotic drug in experimental dosages of 5–9 g/kg of compound feed has an effect on the indicators of nonspecific humoral immunity. Thus, the Russian- Lena sturgeon, grown on compound feeds with probiotic on enterosorbent, had an increased level of BABS and the absence of IMD of individuals. In addition, the probiotic contributed to a decrease in the concentration of nonspecific immune complexes in the blood serum and immunocompetent organs of the Russian-Lena sturgeon, and the results of the analysis for SRB allowed us to conclude that the drug used does not cause inflammatory reactions in the body of sturgeon fish.

Inhibitory effect of Bacillus velezensis 1273 strain cell-free supernatant against developing and preformed biofilms of Staphylococcus aureus and MRSA

Microbial biofilms constitute a significant virulence factor and a substantial challenge in clinical environments due to their role in promoting antimicrobial resistance and their resilience to eradication efforts. Methicillin-resistant Staphylococcus aureus (MRSA) infections substantially increase healthcare costs, extend hospitalizations, and elevate morbidity and mortality rates. Therefore, developing innovative strategies to target and eliminate these bacteria and their biofilms effectively is imperative for robust epidemiological control. In this study, we evaluated the antibacterial and antibiofilm activities of cell-free supernatant (CFS) obtained from the Bacillus velezensis 1273 strain culture. Our data showed that CFS inhibited the growth of S. aureus ATCC 29213 and MRSA (clinical strain), with greater efficacy observed against S. aureus (1:16 dilution). Furthermore, CFS showed substantial potential in reducing biofilm formation in both strains (∼30 %) at subinhibitory concentrations. Additionally, the antibacterial activity against biofilm-formed cells showed that pure CFS treatment decreased the viability of S. aureus (60 %) and MRSA (45 %) sessile cells. We further demonstrated that CFS treatment induces the production of reactive oxygen species (ROS) and damages the membranes and cell walls of the pathogen cells. Genome analysis revealed the presence of genes encoding bacteriocins and secondary metabolites with antibacterial activity in the B. velezensis 1273 genome. These findings highlight the potential of probiotic bacterial metabolites as antibiofilm and anti-multidrug-resistant pathogens.

Synthesis and Characterization of ZnO Nanoparticles by Pulsed Laser Ablation in Liquid Using Different Wavelengths for Antibacterial Application

In this paper, the synthesis of colloidal solution of ZnO nanoparticles by PLAL using an Nd: YAG laser with 1064 nm and 532 nm wavelengths is described. The optical, morphological, structural, wettability and antibacterial activities were studied. The XRD analysis showed the hexagonal wurtzite structure while the UV-vis indicated the blue shift of the absorption peak due to the surface plasmon of the nanoparticle, which showed significant changes in color behavior. The FE-SEM revealed a uniformed spherical shape with a partial size range of 20.50–21.48 nm for ZnO at 1064 and 57.08–59.87 nm for ZnO at 532nm. Also, the concentration measurement indicated that the concentration of ZnO prepared at 1064 nm is 26.7 μg ml-1 and 63 μg ml-1 at 532 nm due to the relevance of high energy to the Zn plate and little distortion in the water and high absorption of short wavelength. Finally, the optical density of the antibacterial activity has been investigated, and both concentrations have good antibacterial activity at 12 h. The ZnO prepared at 532 nm has higher antibacterial activity because it has a high concentration of nanoparticles for both S. aureus and E. coli. Finally, the cell viability for ZnO synthesis with both 1064 nm and 532 nm indicates that this material has high biocompatibility and could be used for medical applications.

Optical Characteristics and Antibacterial Activity of PVA/ZnO Nanocomposites

The process of solution casting was used to create nanocomposites with different amounts of Zinc Oxide nanoparticles (0.001, 0.002, 0.003, 0.004 and 0.005)g. The structural and optical properties of PVA/ZnO nanocomposites were examined.Scanning electron microscopy (SEM) of (PVA/ZnO) nanocomposite films at 0.003 g and 0.005 g shows ZnONPs appear to form groups and disperse well; for the quantity of ZnONPs to (PVA) polymer, it forms varied shapes in specific areas inside the polymer . UV-Visible spectroscopy was utilized to measure the optical properties in the (200-900) nm wavelength range. Experiments have shown that increasing the amount of ZnONPs in nanocomposites enhances the absorbance spectrum and absorption coefficient of PVA polymer. The energy band gap of PVA polymer decreased as the amount of ZnONPs grew. In a research of the antibacterial activity of these nanocomposites, pathogen microorganisms such as Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella similipneumoniae, and Candida albicans were utilized. According to the findings, the chemical nature and shape of the composites have a substantial impact on antibacterial activity, with antibacterial activity increasing as the amount of Zinc Oxide rise.

Multiplex antimicrobial activities of the self-assembled amphiphilic polypeptide β nanofiber KF-5 against vaginal pathogens

BackgroundVaginal infections caused by multidrug-resistant pathogens such as Candida albicans and Gardnerella spp. represent a significant health challenge. Current treatments often fail because of resistance and toxicity. This study aimed to synthesize and characterize a novel amphiphilic polypeptide, KF-5, and evaluate its antibacterial and antifungal activities, biocompatibility, and potential mechanisms of action.ResultsThe KF-5 peptide was synthesized via solid-phase peptide synthesis and self-assembled into nanostructures with filamentous and hydrogel-like configurations. Characterization by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) confirmed the unique nanostructural properties of KF-5. KF-5 (125, 250, or 500 µg/ml) demonstrated potent antibacterial and antifungal activities, with significant inhibitory effects on drug-resistant Candida albicans and Gardnerella spp. (P < 0.05). In vitro assays revealed that 500 µg/ml KF-5 disrupted microbial cell membranes, increased membrane permeability, and induced lipid oxidation, leading to cell death (P < 0.05). Cytotoxicity tests revealed minimal toxicity in human vaginal epithelial cells, keratinocytes, and macrophages, with over 95% viability at high concentrations. Molecular dynamics simulations indicated that KF-5 interacts with phospholipid bilayers through electrostatic interactions, causing membrane disruption. In vivo studies using a mouse model of vaginal infection revealed that 0.5, 1, and 2 mg/ml KF-5 significantly reduced fungal burden and inflammation, and histological analysis confirmed the restoration of vaginal mucosal integrity (P < 0.01). Compared with conventional antifungal treatments such as miconazole, KF-5 exhibited superior efficacy (P < 0.01).ConclusionsKF-5 demonstrates significant potential as a safe and effective antimicrobial agent for treating vaginal infections. Its ability to disrupt microbial membranes while maintaining biocompatibility with human cells highlights its potential for clinical application. These findings provide a foundation for further development of KF-5 as a therapeutic option for combating drug-resistant infections.

New Isocoumarins from An Endophytic Fungal Strain Diaporthe arengae M2 and Their Antibacterial Activities.

Four new isocoumarin derivatives 12-O-acetyl-isocitreoisocoumarinol (1), (+)-(10R)-O-acetyl-diaportinol (2-a), (-)-(10S)-O-acetyl-diaportinol (2-b), peyroisocoumarin E (3) and new stereoconfigurations of three isocoumarin derivatives desmethyldichlorodiaportinol A (4), threo-monochlorodiaportinol A (5-a), erytheo-monochlorodiaportinol A (5-b), together with nine known ones (6-14), were separated from the rice fermentation of endophytic fungus Diaporthe arengae M2 isolated from Camellia oleifera. The structures of new compounds were determined by extensive spectroscopic analyses including nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Compounds 4, 7, 8, 12, 13 exhibited definite inhibition against five strains of bacteria with the MIC values range from 16 μg/mL to 64 μg/mL.

High-Throughput Discovery of Synthetic Siderophores for Trojan Horse Antibiotics.

To cause infection, bacterial pathogens must overcome host immune factors and barriers to nutrient acquisition. Reproducing these aspects of host physiology in vitro has shown great promise for antibacterial drug discovery. When used as a bacterial growth medium, human serum replicates several aspects of the host environment, including innate immunity and iron limitation. We previously reported that a high-throughput chemical screen using serum as the growth medium enabled the discovery of novel growth inhibitors overlooked by conventional screens. Here, we report that a subset of compounds from this high-throughput serum screen display an unexpected growth enhancing phenotype and are enriched for synthetic siderophores. We selected 35 compounds of diverse chemical structure and quantified their ability to enhance bacterial growth in human serum. We show that many of these compounds chelate iron, suggesting they were acting as siderophores and providing iron to the bacteria. For two different pharmacophores represented among these synthetic siderophores, conjugation to the β-lactam antibiotic ampicillin imparted iron-dependent enhancement in antibacterial activity. Conjugation of the most potent growth-enhancing synthetic siderophore with the monobactam aztreonam produced MLEB-22043, a broad-spectrum antibiotic with significantly improved activity against Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. This synthetic siderophore-monobactam conjugate uses multiple TonB-dependent transporters for uptake into P. aeruginosa. Like aztreonam, MLEB-22043 demonstrated activity against metallo-β-lactamase expressing bacteria, and, when combined with the β-lactamase inhibitor avibactam, was active against clinical strains coexpressing the NDM-1 metallo-β-lactamase and serine β-lactamases. Our work shows that human serum is an effective bacterial growth medium for the high-throughput discovery of synthetic siderophores, enabling the development of novel Trojan Horse antibiotics.

Evaluation of the Antibacterial Activity of Antibiotics with different Antibacterial Mechanisms using Electrochemical Signals of Heat‐Treated Escherichia Coli

AbstractElectrochemistry with purines as indicators may be a promising new method for antibiotic activity testing. However, the traditional electrochemical detection method (S‐LSV) requires a long accumulation time for purines and has low signal intensity. High‐temperature treatment of bacterial samples may significantly enhance the signal intensity and speed of detection. However, this process may also impact the structure and metabolism of bacteria. Further research is necessary to determine how electrochemical signals respond to antibiotic antibacterial activity. In this paper, the electrochemical detection method based on heat‐treated Escherichia coli (E. coli, H‐LSV) was used to investigate the effects of 11 antibiotics with four different antibacterial mechanisms on the electrochemical behavior of E. coli. The results showed that compared to the S‐LSV, the electrochemical signal of E. coli detected by the H‐LSV increased by 362%, and showed a strong linear relationship with bacterial counts up to 1.88×108 CFU/mL, with a detection limit of 1.15×106 CFU/mL. The electrochemical signal consistently correlated with changes in viable E. coli counts following treatment with the four different antibacterial mechanisms. HPLC analysis further confirmed that the changes in purine contents in bacteria after antibiotic treatment were consistent with the trends in electrochemical signals. The evaluation of antibiotic antibacterial ability by H‐LSV showed good consistency with results from plate counting and turbidity methods, but was closer to the results of plate counting. The inhibition rates of antibiotics on E. coli detected by H‐LSV and S‐LSV also showed high consistency, indicating that short‐term high‐temperature treatment of E. coli did not affect the response of the bacterium to the inhibitory activity of antibiotics.

Co(II), Ni(II), and Cu(II) Ternary Complexes With 2,6‐Pyridinedicarboxylic Acid and 2,2′‐Bipyridyl: Synthesis, Characterization, DNA Binding, Photo‐Cleavage, and Antimicrobial Studies

ABSTRACTThe interaction of 2,6‐pyridinedicarboxylicacid (PDA) and 2,2′‐bipyridyl (Bipy) with Co(II), Ni(II), and Cu(II) ions produced new ternary complexes [M (PDA)(Bipy)(H2O)] (M = Co(II), Ni(II), and Cu(II)), which were studied by elemental, spectral (FT‐IR, Mass, UV–Vis), and thermal analysis, and their interaction with Ct‐DNA was thoroughly studied using various methods, including absorption spectroscopy, fluorescence spectroscopy, and viscosity measurements. Spectrophotometric titration and viscosity measurements indicated that all the complexes bind to DNA via the groove mode of binding. The salt‐dependent binding of ternary metal complexes to Ct‐DNA has been studied by a UV–Vis spectrophotometric titration experiment. Furthermore, photocleavage studies were used to examine how the metal complexes interacted with the pBR322 DNA, and the results proved that these compounds have obvious photo cleavage properties. The biological effects were studied by antibacterial activity.