Spectrum Of Antibacterial Activity Research Articles

Concise Synthesis of Pseudane IX, Its N-Oxide, and Novel Carboxamide Analogs with Antibacterial Activity

A four-step synthesis of the natural product pseudane IX, starting from 3-oxododecanoic acid phenylamide and including only one chromatographic purification, was accomplished with an overall yield of 52%. The same synthetic sequence, but with a controlled partial reduction of a nitro group in the penultimate intermediate, led to the N-oxide of pseudane IX (NQNO). A shortened three-step variation of the synthesis allowed for the preparation of novel carboxamide analogs of the natural product. An agar diffusion assay against six different bacterial strains revealed significant antibacterial activity of the novel analogs against S. aureus at a concentration of 100 µg/mL. One of the novel compounds showed a remarkably broad spectrum of antibacterial activity, comparable to that of the positive control NQNO.

Dietary supplementation with a novel acidifier sodium diformate improves growth performance by increasing growth-related hormones levels and prevents Salmonella enterica serovar Pullorum infection in chickens.

Since the use of antibiotics as growth promoters in animal feed has been restricted or banned in several countries, finding suitable alternatives is crucial for maintaining animal health. In this study, a novel formate acidifier named sodium diformate (NaDF) was synthesized, and the effects on growth performance and the prevention effects against Salmonella enterica serovar Pullorum infections in chickens were assessed. In broilers, NaDF supplementation improved growth performance, as evidenced by increased body weights and reduced feed conversion ratios. At 38 days of age, NaDF supplementation increased the levels of growth-hormone and ghrelin in the serum, lowered pH values in the gut, improved duodenal morphology, as shown by increased villus length/crypt depth ratios. NaDF also modulated the abundance of beneficial and harmful bacteria without changing the general microbiota diversity and short-chain fatty acids levels, which would be beneficial for maintaining gut homeostasis during its use. NaDF exhibited a broad spectrum of antibacterial activity in vitro. Supplementation with NaDF effectively decreased S. Pullorum colonization in the cecum, liver and spleen in chickens, and mitigated pathological changes in the tissues. Therefore, as a novel acidifier, NaDF can improve chicken growth performance by increasing growth-related hormones levels while maintaining the diversity of gut microbiota, and also resist intestinal bacterial infection. These results provided evidences for the application of NaDF as an effective and safe animal feed in poultry farming.

Biochemical characterisation and production kinetics of high molecular-weight (HMW) putative antibacterial proteins of insect pathogenic Brevibacillus laterosporus isolates

BackgroundBacterial genomes often encode structures similar to phage capsids (encapsulins) and phage tails which can be induced spontaneously or using genotoxic compounds such as mitomycin C. These high molecular-weight (HMW) putative antibacterial proteins (ABPs) are used against the competitive strains under natural environment. Previously, it was unknown whether these HMW putative ABPs originating from the insect pathogenic Gram-positive, spore-forming bacterium Brevibacillus laterosporus (Bl) isolates (1821L, 1951) are spontaneously induced during the growth and pose a detrimental effect on their own survival. Furthermore, no prior work has been undertaken to determine their biochemical characteristics.ResultsUsing a soft agar overlay method with polyethylene glycol precipitation, a narrow spectrum of bioactivity was found from the precipitated lysate of Bl 1951. Electron micrographs of mitomycin C- induced filtrates showed structures similar to phage capsids and contractile tails. Bioactivity assays of cell free supernatants (CFS) extracted during the growth of Bl 1821L and Bl 1951 suggested spontaneous induction of these HMW putative ABPs with an autocidal activity. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of spontaneously induced putative ABPs showed appearance of ~ 30 kDa and ~ 48 kDa bands of varying intensity across all the time intervals during the bacterial growth except in the initial hours. Statistically, spontaneously induced HMW putative ABPs of Bl 1951 exhibited a significant decrease in the number of viable cells of its producer strain after 18 h of growth in liquid. In addition, a significant change in pH and prominent bioactivity of the CFS of this particular time period was noted. Biochemically, the filtered supernatant derived from either Bl 1821L or Bl 1951 maintained bioactivity over a wide range of pH and temperature.ConclusionThis study reports the spontaneous induction of HMW putative ABPs (bacteriocins) of Bl 1821L and Bl 1951 isolates during the course of growth with potential autocidal activity which is critically important during production as a potential biopesticide. A narrow spectrum of putative antibacterial activity of Bl 1951 precipitate was found. The stability of HMW putative ABPs of Bl 1821L and Bl 1951 over a wide range of pH and temperature can be useful in expanding the potential of this useful bacterium beyond the insecticidal value.

Highly Compressible, Superabsorbent, and Biocompatible Hybrid Cryogel Constructs Comprising Functionalized Chitosan and St. John's Wort Extract.

Biobased porous hydrogels enriched with phytocompounds-rich herbal extracts have aroused great interest in recent years, especially in healthcare. In this study, new macroporous hybrid cryogel constructs comprising thiourea-containing chitosan (CSTU) derivative and a Hypericum perforatum L. extract (HYPE), commonly known as St John's wort, were prepared by a facile one-pot ice-templating strategy. Benefiting from the strong interactions between the functional groups of the CSTU matrix and those of polyphenols in HYPE, the hybrid cryogels possess excellent liquid absorption capacity, mechanical resilience, antioxidant performance, and a broad spectrum of antibacterial activity simultaneously. Thus, owing to their design, the hybrid constructs exhibit an interconnected porous architecture with the ability to absorb over 33 and 136 times their dry weight, respectively, when contacted with a phosphate buffer solution (pH 7.4) and an acidic aqueous solution (pH 2). These cryogel constructs have extremely high compressive strengths ranging from 839 to 1045 kPa and withstand elevated strains of over 70% without developing fractures. Moreover, the water-swollen hybrid cryogels with the highest HYPE content revealed a complete and instant shape recovery after uniaxial compression. The incorporation of HYPE into CSTU cryogels enabled substantial improvement in scavenging reactive oxygen species and an expanded antibacterial spectrum toward multiple pathogens, including Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and fungi (Candida albicans). Cell viability experiments demonstrated the cytocompatibility of the 3D cryogel constructs, which did not induce changes in the fibroblast morphology. This work showcases a simple and effective strategy to immobilize HYPE extracts on CSTU 3D networks, allowing the development of novel multifunctional platforms with promising potential in hemostasis, wound dressing, and dermal regeneration scaffolds.

The Ocular Chloramphenicol Story

Chloramphenicol eye drops and ointment are the most used ocular antibiotic worldwide. Chloramphenicol was discovered in 1947 and was only the third antibiotic to successfully be produced and only the first antibiotic suitable for large-scale commercial production. By the 1950s, the drug had been developed into drop and ointment forms. The broad spectrum of anti-bacterial activity of Chloramphenicol led to widespread use. Ocular Chloramphenicol remains an important weapon in the ophthalmic armamentarium despite emergence of evidence of possible side effects in the 1970s. This is a short review of the remarkable story of the discovery, development and tribulations of ocular Chloramphenicol. Keywords: History; Chloramphenicol Abbreviations: FDA: Food and Drug Administration

A novel cathelicidin TS-CATH derived from Thamnophis sirtalis combats drug-resistant gram-negative bacteria in vitro and in vivo

Antimicrobial peptides are promising therapeutic agents for treating drug-resistant bacterial disease due to their broad-spectrum antimicrobial activity and decreased susceptibility to evolutionary resistance. In this study, three novel cathelicidin antimicrobial peptides were identified from Thamnophis sirtalis, Balaenoptera musculus, and Lipotes vexillifer by protein database mining and sequence alignment and were subsequently named TS-CATH, BM-CATH, and LV-CATH, respectively. All three peptides exhibited satisfactory antibacterial activity and broad antibacterial spectra against clinically isolated E. coli, P. aeruginosa, K. pneumoniae, and A. baumannii in vitro. Among them, TS-CATH displayed the best antimicrobial/bactericidal activity, with a rapid elimination efficiency against the tested drug-resistant gram-negative bacteria within 20 min, and exhibited the lowest cytotoxicity toward mammalian cells. Furthermore, TS-CATH effectively enhanced the survival rate of mice with ceftazidime-resistant E. coli bacteremia and promoted wound healing in meropenem-resistant P. aeruginosa infection. These results were achieved through the eradication of bacterial growth in target organs and wounds, further inhibiting the systemic dissemination of bacteria and the inflammatory response. TS-CATH exhibited direct antimicrobial activity by damaging the inner and outer membranes, resulting in leakage of the bacterial contents at super-MICs. Moreover, TS-CATH disrupted the bacterial respiratory chain, which inhibited ATP synthesis and induced ROS formation, significantly contributing to its antibacterial efficacy at sub-MICs. Overall, TS-CATH has potential for use as an antibacterial agent.

Новий метаболіт Myrothecium cinctum 910 трихотеценової природи та його біологічні властивості

Fungi of the Myrothecium genus are well-known producers of macrocyclic trichothecenes, characterized by the acute toxic effect on warm-blooded organisms and fungicidal action against a wide range of fungi. At the same time, as established by us earlier, M. cinctum (current name Striaticonidium cinctum) 910 shows a wide spectrum of antibacterial activity: along with antifungal activity against mycelial, yeast-like and phytopathogenic test-cultures it strongly inhibited the growth of gram-positive test-strains and to lesser extend – the growth of gram-negative and phytopathogenic bacteria. This strain also revealed significant phytotoxic potential suppressing the growth of green algae Chlorella strains. The aim of the work was to isolate, to purify and to obtain in crystalline form the biological active metabolites of M. cinctum 910 and to study their physicochemical characteristics and biological activity. Methods. To obtain biologically active metabolites in the purified crystalline form, the extraction followed by separation by column chromatography and recrystallization was used; physicochemical methods and microbiological tests were used for characterization of their properties. Results. Three substances which showed the wide spectrum of biological activity to indicator test-cultures were obtained in crystalline form: preparation МС910 with high antibiotic activity and preparations from fractions 8/2 and 9 with high antifungal and phytotoxic activities. Taking into account the data of spectroscopy in the UV-range of spectrum, of spectrums of antibiotic activity and of qualitative reaction with 4-(4-nitrobenzyl)pyridine, it can be concluded that active fractions 8/2 and 9 contain macrocyclic trichothecenes whereas the metabolite МС910 (which is proved by data of IR-spectroscopy) belongs to simple trichothecenes – substances like to macrocyclic trichothecenes but without macrocyclic fragment in their structure. Conclusions. Antibiotic properties of M. cinctum 910 are due to the complex of biological active metabolites with different biological and physicochemical properties. In view on the biological activity of MC910, it can be argued that it has atypical for trichothecenes, including macrocyclc trichothecenes, antibacterial properties as well as it is non-toxic and does not reveal dermatocidal activity in studied concentrations. Therefore, we assume that MC910 is new, not described earlier metabolite of trichothecene nature, which needs further studies. At the same time, active metabolites from fractions 8/2 and 9 are represented by macrocyclic trichothecenes, which is also indicated by the spectra of their biological activity.

Fabrication and antimicrobial properties of novel meropenem-honey encapsulated chitosan nanoparticles against multiresistant and biofilm-forming Staphylococcus aureus as a new antimicrobial agent.

Honey exhibits a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) ones. Chitosan (Cs) is a mucoadhesive polymer that also has antibacterial properties. Special attention has been paid to the design of polymeric nanoparticles (NPs) as new nano drug delivery systems to overcome bacterial resistance and its problems. The aim of the present study is to synthesize Cs-meropenem NPs with/without honey as an antibiofilm and antibacterial agent to inhibit Staphylococcus aureus. This study synthesized meropenem and honey-loaded Cs nanogels and subsequently characterized them by Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared Spectroscopy (FTIR), and DLS-zeta potential. Using the broth microdilution and crystal violet assays, the antibacterial and antibiofilm activity of meropenem and honey-loaded Cs nanogel, free meropenem, free honey, and free Cs NPs were investigated in vitro against MRSA strains. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) was also used to test the cytotoxicity of several Cs-NPs compound against the HEK-293 regular cell line. The average size of meropenem and honey-Cs-NPs was reported to be 119.885nm, and encapsulation efficiency was 88.33 ± 0.97 with stability up to 60 days at 4°C. The NPs showed enhanced antibiofilm efficacy against S. aureus at sub-minimum inhibitory concentrations. Additionally, the cytotoxicity of meropenem and honey-encapsulated Cs against the HEK-293 normal cell line was insignificant. Our findings suggested that meropenem and honey-Cs-NPs might be potential antibacterial and antibiofilm materials.

Pharmacokinetics and Preclinical Safety Studies of Modified Endolysin-based Gel for Topical Application

Antibacterial therapy with phage-encoded endolysins or their modified derivatives with improved antibacterial, biochemical and pharmacokinetic properties is one of the most promising strategies that can supply existing antibacterial drugs array. Gram-negative bacteria-induced infections treatment is especially challenging because of rapidly spreading bacterial resistance. We have developed modified endolysin LysECD7-SMAP with a significant antibacterial activity and broad spectra of action against gram-negative bacteria. Endolysin was formulated in a bactericidal gel for topical application with pronounced effectivity in local animal infectious models. Here we present preclinical safety studies and pharmacokinetics of LysECD7-SMAP-based gel. We have detected LysECD7-SMAP in the skin and underlying muscle at therapeutic concentrations when the gel is applied topically to intact or injured skin. Moreover, the protein does not enter the bloodstream, and has no systemic bioavailability, assuming no systemic adverse effects. In studies of general toxicology, local tolerance, and immunotoxicology it was approved that LysECD7-SMAP gel local application results in the absence of toxic effects after single and multiple administration. Thus, LysECD7-SMAP-containing gel has appropriate pharmacokinetics and can be considered as safe that supports the initiation of the phase I clinical trials of novel antibacterial drug intending to treat acute wound infections caused by resistant gram-negative bacteria.

Enhanced biodegradation of sulfamethoxazole by pyrogenic carbon derived from aquacultural waste sludge

Sulfamethoxazole (SMX) is a widely utilized antibiotic that exhibits a broad spectrum of antibacterial activity, but its inadvertent release into the environment poses a significant threat to human society. The inefficacy of SMX degradation in microbial pipelines constantly challenges the regulation of antibiotics, making it a pressing and compelling concern. Former research has demonstrated the enhancement of the waste sludge-derived materials on SMX biodegradation, but the impact of these materials on microbial behavior remains unclear. In this study, two pyrogenic carbon materials (FBC and RBC) were prepared from aquacultural waste sludge and its downstream river sediment, respectively, to collaborate with SMX degrading species, Alcaligenes sp., for highly efficient removal of SMX. The cells of Alcaligenes sp. successfully colonized onto the biocompatible surface of the materials, and this hybrid structure nearly doubled the SMX degradation efficiency of the group without the carbon materials. The transcriptome analysis revealed that the existence of carbon materials significantly upregulated the expression of SMX degrading-related genes, including metCF and paaCIK, which led to bond breaking and benzene ring breakdown for the degradation of sulfamethoxazole. This work provides new insights into the mechanisms and environmental significance of SMX degradation by microbial immobilization onto waste-derived carbon-rich materials.

A magnetic nanozyme platform for bacterial colorimetric detection and chemodynamic/photothermal synergistic antibacterial therapy.

Rapid, convenient, and sensitive detection of bacteria and development of novel antibacterial materials are conducive to accurate treatment of bacterial infection and reducing the generation of drug-resistant bacteria caused by overuse of antibiotics. A dual-function magnetic nanozyme, Fc-MBL@rGO@Fe3O4, has been constructed with broad-spectrum bacterial affinity and good peroxidase-like activity. Detection signal amplification was realized in the presence of 3,3',5,5'-tetramethylbenzidine (TMB) with a detection limit of 26 CFU/mL. In addition, the excellent photothermal properties of Fc-MBL@rGO@Fe3O4 could realize synergistic chemodynamic/photothermal antibacterial therapy. Furthermore, the good bacterial affinity of Fc-MBL@rGO@Fe3O4 enhances the accurate and rapid attack of hydroxyl radical (·OH) on the bacterial membrane and achieves efficient sterilization (100%) at low concentration (40µg/mL) and mild temperature (47℃). Notably, Fc-MBL@rGO@Fe3O4 has a broad spectrum of antibacterial activity against Gram-negative, Gram-positive, and drug-resistant bacteria. The magnetic nanoplatform integrating detection-sterilization not only meets the need for highly sensitive and accurate detection in different scenarios, but can realize low power density NIR-II light-responsive chemodynamic/photothermal antibacterial therapy, which has broad application prospects.

Exploring the genetic basis of natural resistance to microcins.

Enterobacteriaceae produce an arsenal of antimicrobial compounds including microcins, ribosomally produced antimicrobial peptides showing diverse structures and mechanisms of action. Microcins target close relatives of the producing strain to promote its survival. Their narrow spectrum of antibacterial activity makes them a promising alternative to conventional antibiotics, as it should decrease the probability of resistance dissemination and collateral damage to the host's microbiota. To assess the therapeutic potential of microcins, there is a need to understand the mechanisms of resistance to these molecules. In this study, we performed genomic analyses of the resistance to four microcins [microcin C, a nucleotide peptide; microcin J25, a lasso peptide; microcin B17, a linear azol(in)e-containing peptide; and microcin E492, a siderophore peptide] on a collection of 54 Enterobacteriaceae from three species: Escherichia coli, Salmonella enterica and Klebsiella pneumoniae. A gene-targeted analysis revealed that about half of the microcin-resistant strains presented mutations of genes involved in the microcin mechanism of action, especially those involved in their uptake (fhuA, fepA, cirA and ompF). A genome-wide association study did not reveal any significant correlations, yet relevant genetic elements were associated with microcin resistance. These were involved in stress responses, biofilm formation, transport systems and acquisition of immunity genes. Additionally, microcin-resistant strains exhibited several mutations within genes involved in specific metabolic pathways, especially for S. enterica and K. pneumoniae.

Antibacterial Activity of Herbal Essential Oils against Gram-positive and Gram-negative Bacteria with a Potential for Multidrug Resistance

Background: In recent years, there has been an extensive and great interest in researching and developing alternative antibacterial agents from various sources to combat bacterial resistance. Therefore, greater attention has been paid to the screening of antibacterial activity. Aims: This study evaluated different types of herbal essential oil to inhibit the growth of selected human pathogenic bacteria with potential multidrug resistance properties. Methodology: The herbal essential oils used include thyme oil, tea tree oil, bergamot oil and lavender oil against Staphylococcus aureus, Escherichia coli and Bacillus subtilis. Antibacterial screening of all the essential oils was done by disk diffusion method. Results: Herbal essential oils have exhibited a broad spectrum of antibacterial activities against the selected microbes: B. subtilis, S. aureus and E. coli. Thyme oil has the most potential antibacterial properties for B. subtilis(40 mm), followed by S. aureus(35 mm) and E. coli(35 mm). Both bergamot and lavender oils showed higher antibacterial effects for E. coli and B. subtilis but have lower efficacy with S. aureus than tea tree oil. Conclusion: The herbal essential oils used in this study can serve as a source of alternative antibacterial agents and may play an important role in the discovery of new drugs for the treatment of a wide range of pathogenic bacteria in the future.

Comparison Between Moxifloxacin and Chloramphenicol for the Treatment of Bacterial Eye Infections

Background: Moxifloxacin is a bactericidal methoxyquinolone used for the treatment of conjunctivitis and prophylactic therapy in cataract and refractive surgeries. Chloramphenicol is a bacteriostatic organochlorine introduced into clinical practice in 1948 and used mainly in topical preparations because of its known toxicity. Objectives: The study aimed to evaluate the in vitro antibacterial effect and the ocular cytotoxicity of these broad-spectrum antibiotics. Methods: Antimicrobic activity was tested on four bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis), and determined through calculation of Minimum Inhibitory Concentration (MIC) and IC50 for each microorganism. Antibacterial activity was determined by microdilution method after 24 hours incubation with 2-fold serial dilutions (2.5 mg/ml to 4.883 µg/ml) of moxifloxacin and chloramphenicol. Disk diffusion test were performed according to EUCAST methodology. Biofilm formation inhibition (BIC) and biofilm Eradication Concentration (BEC) assay were conducted for P. aeruginosa and S. epidermidis using the microdilution method. Cytotoxicity of antibiotics was evaluated by MTT colorimetric assay on human corneal cell (HCE-2). Results: Cytotoxicity of antibiotics was evaluated on human epithelial corneal cells after 4 hours treatment by viability assay. Results showed that corneal cell viability was significantly higher after moxifloxacin treatment compared to Chloramphenicol (p<0.01). Moxifloxacin is characterized by a significantly lower MIC and IC50 values and a larger inhibition zone for all the strain tested, with high performance in controlling gram-negative growth, compared to Chloramphenicol. Moreover, Moxifloxacin showed higher activity compared to Chloramphenicol in the inhibition of biofilm formation and in the disruption of biofilm, especially against S. epidermidis biofilm. Conclusions: The lower corneal cell toxicity and the broader spectrum of antibacterial activity observed with Moxifloxacin suggests its use in ophthalmic solution for the treatment of bacterial eye infections.

Study of Molecular Parameters and Antibacterial Activity of a Peptide Preparation Derived from Human Leukocytes

Background. The study of new antimicrobial substances isolated from the living organism tissues is of particular importance for medicine and the biopharmaceutical industry. Leukocyte peptides can act as an alternative to traditional antibiotics to overcome the bacterial antibiotic resistance problem.Aim. Evaluation of molecular weight and biological activity of ultrasound-derived leukocyte peptides.Methods. Separation of leukocyte peptide complexes into particular fractions by reverse phase chromatography and evaluation of their antibacterial activity by serial dilution and diffusion methods.Results. Studies have shown that one peptide fraction with a molecular weight of 440–570 Da has pronounced antibacterial activity.Conclusion. The obtained experimental data testify to the high therapeutic potential of the leukocyte protein-peptide complex, which has a wide spectrum of antibacterial activity.

Evaluation of probiotic bifidobacteria strains from Iranian traditional dairy products for their anti-hyperlipidemic potential.

This study investigated the therapeutic potential of probiotic bifidobacteria, isolated from Iranian fermented dairy products, in a hyperlipidemic animal model. Bifidobacterium strains were extracted from traditional dairy samples and screened using physiological and phenotypic examinations, 16S rRNA analysis, and probiotic properties such as tolerance to gastrointestinal juice, antimicrobial activity, and antibiotic susceptibility. The ability of the screened bifidobacteria to reduce serum and liver lipids in vivo was tested using male Wistar rats. Six strains of bifidobacteria were isolated from traditional Iranian fermented dairy. These strains showed promising in vitro activity in lowering triglyceride and cholesterol, tolerance to simulated gastrointestinal juice, the ability to adhere to Caco-2 cells, acceptable antibiotic susceptibility, and a broad spectrum of antibacterial activity. The diet supplemented with isolated bifidobacteria significantly reduced serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), liver tissue lipid levels, and hepatic enzymes in animals when compared to a high-fat diet without strains (p < 0.01). Additionally, the potential probiotic-supplemented diet significantly increased bile acid excretion in the feces and upregulated hepatic CYP7A1 expression levels (p < 0.05), while NPC1L1, ACAT2, and MTP gene expressions in small intestinal cells were downregulated (p < 0.05). Bifidobacteria isolated from Iranian traditional dairy showed potential for use in the production of fermented foods that have hypolipemic activity in the host.

Insight into the inhibitory activity and mechanism of bovine cathelicidin BMAP 27 against Salmonella Typhimurium

This study synthesized an antimicrobial peptide based on the bovine cathelicidin BMAP 27 sequence. It was found to have a broad spectrum of antibacterial activity, with exceptionally high activity against Salmonella. However, the antibacterial mechanism of BMAP 27 against Salmonella remains unclear. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of BMAP 27 against Salmonella enterica serovar Typhimurium were determined to be 2 μM and 4 μM, respectively. After treatment with 2 MIC of BMAP 27, the absorbance of DNA in centrifugal supernatant increased from 0.244 to 1.464, and that of protein rose from 0.174 to 0.774, respectively. BMAP 27 has compromised the cell membrane as observed through field emission scanning electron microscope (FESEM) and transmission electron microscopy (TEM), and confirmed by the propidium iodide (PI) test. The alkaline phosphatase (AKP) enzyme activity in the supernatant of the 2 MIC treatment group was 2.15 times higher than the control group, indicating extracellular membrane damage. BMAP 27 treatment increased intracellular ROS levels as tested by dichlorofluorescein diacetate (DCFH) staining. DNA interaction analysis revealed that BMAP 27 has a binding affinity towards DNA, causing its characteristic bands to disappear and peak intensity at 260 nm to reduce. Molecular docking identified its potential binding mode with DNA. The crystal violet biofilm staining results demonstrated that BMAP 27 inhibited S. Typhimurium biofilm formation by 43.1 % and cleared mature biofilms by 53.62 %. Confocal Laser scanning electron microscopy (CLSM) observed that BMAP 27 could kill bacteria within the biofilm and dislodge bacteria from the surface of glasses. Swimming tests identified that the motor capacity of S. Typhimurium was diminished by BMAP 27. By counting the total bacteria, BMAP 27 was revealed to exert bacteriostatic effects in chilled pork and orange juice, which might provide a basis for its application in the inhibition of Salmonella.

Synthesis of New Derivatives of Berberine Canagliflozin and Study of Their Antibacterial Activity and Mechanism.

The isoquinoline alkaloid berberine, derived from Coptidis rhizoma, exhibits antibacterial, hypoglycemic, and anti-inflammatory properties. Canagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. We synthesized compounds B9OC and B9OBU by conjugating canagliflozin and n-butane at the C9 position of berberine, aiming to develop antimicrobial agents for combating bacterial infections worldwide. We utilized clinically prevalent pathogenic bacteria, namely Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, to investigate the antibacterial efficacy of B9OC. This was accomplished through the determination of the MIC80 values, analysis of bacterial growth curves, evaluation of biofilm formation using crystal violet staining, assessment of impact on bacterial proteins via SDS-PAGE analysis, and observation of alterations in bacterial morphology utilizing field emission scanning electron microscopy. Meanwhile, the ADMET of compound B9OC was predicted using a computer-aided method. The findings revealed that B9OC exhibited lower minimal inhibitory concentrations against all three bacteria compared to berberine alone or in combination with canagliflozin. The minimal inhibitory concentrations (MICs) of B9OC against the three experimental strains were determined to be 0.035, 0.258, and 0.331 mM. However, B9OBu exhibited a lower level of antimicrobial activity compared to berberine. The compound B9OC exhibits a broad spectrum of antibacterial activity by disrupting the integrity of bacterial cell walls, leading to cellular rupture and the subsequent degradation of intracellular proteins.

Novel drug candidates against antibiotic-resistant microorganisms: A review.

Antibiotic resistance is fast spreading globally, leading to treatment failures and adverse clinical outcomes. This review focuses on the resistance mechanisms of the top five threatening pathogens identified by the World Health Organization's global priority pathogens list: carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin, vancomycin-resistant Staphylococcus aureus. Several novel drug candidates have shown promising results from in vitro and in vivo studies, as well as clinical trials. The novel drugs against carbapenem-resistant bacteria include LCB10-0200, apramycin, and eravacycline, while for Enterobacteriaceae, the drug candidates are LysSAP-26, DDS-04, SPR-206, nitroxoline, cefiderocol, and plazomicin. TNP-209, KBP-7072, and CRS3123 are agents against E. faecium, while Debio 1450, gepotidacin, delafloxacin, and dalbavancin are drugs against antibiotic-resistant S. aureus. In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small molecules with potential antibacterial effects screened by computational receptor docking. As drug discovery progresses, preclinical and clinical studies should also be extensively conducted on the currently available therapeutic agents to unravel their potential antibacterial effect and spectrum of activity, as well as safety and efficacy profiles.

Evaluation of Equisetin as an Anti-Microbial and Herbicidal Agent from Endophytic Fungus Fusarium sp. JDJR1

Equisetin was isolated from endophytic fungus Fusarium sp. JDJR1 via bioassay-guided isolation, and it was evaluated as an anti-microbial and herbicidal agent. Bioactivity assessments revealed that equisetin exhibited a broad spectrum of fungicidal and anti-bacterial activity against various plant pathogens. The EC50 values against Botrytis cinerea, Fusarium graminearum, Sclerotinia sclerotiorum, and Rhizoctonia solani ranged from 10.7 to 21.0 μg/mL. Notably, equisetin demonstrated activity against Xanthomonas oryzae pv. oryzicola, Xanthomonas oryzae pv. oryzae and Pseudomonas solanacearum with an MIC range of 4–16 μg/mL, surpassing the efficacy of the positive control: streptomycin sulfate. Equisetin, at a concentration of 100 μg/mL, could completely inhibit the spore germination of F. graminearum. In in vivo protection experiments, the protective efficacy of equisetin against B. cinerea on tomato fruits at 200 μg/mL reached 72.9%. Furthermore, in herbicidal activity tests that use the Petri dish bioassay method, equisetin had a good inhibitory effect on the root growth of weeds. At a concentration of 100 μg/mL, the inhibition rates for Echinochloa crusgalli and Eclipta prostrata root were 98.8 and 94.4%, respectively.