Potent Antimicrobial Activity Research Articles

An Evaluation of Antimicrobial Activity of Common Zingiber officinale Cultivars Grown in Sri Lanka

Ginger (Zingiber officinale) has long been a therapeutic agent in traditional medicine systems worldwide and is a leading drug candidate in the pharmaceutical industry. In Sri Lanka, many forms of ginger are often used in the food industry, mainly as a spice; it also plays a vital role in the Ayurvedic medicine system. This study evaluated the antimicrobial activity of the two most cultivated cultivars of Zingiber officinale in Sri Lanka, the Sri Lankan (TG) and Chinese (CG) cultivars. Two types of extracts (ethanol and aqueous) were obtained from the rhizomes of each cultivar. The potential antimicrobial activity of the extracts was tested against three types of pathogenic test organisms, Staphylococcus aureus ATCC 25923, Salmonella typhi DSM 17058, and Escherichia coli ATCC 25922, using the agar well diffusion method along with positive control, chloramphenicol, and negative controls, 95% ethanol or distilled water. In conclusion, both Zingiber officinale cultivars exhibit varying antimicrobial potential, with ethanol extracts showing stronger activity than aqueous ones. None of the extracts was effective against Escherichia coli. The agar dilution method determined the minimum inhibitory concentration (MIC) of each ginger extract. Among the extracts, ethanol extracts showed higher effectivity than aqueous extracts, where all test organisms showed inhibition at a concentration of 20 mg/mL. The antimicrobial activity of the Chinese cultivar outperforms the Sri Lankan cultivar against target organisms, Salmonella typhi, and Staphylococcus aureus.

Antimicrobial activity of magnolol against Bacillus cereus and its application as food preservative

The aim of this study was to explore the antibacterial properties and mechanism of magnolol against Bacillus cereus. Our findings demonstrated that magnolol exhibited potent antimicrobial activity against B. cereus, with minimum inhibitory concentrations (MICs) of 2 μg/mL. Additionally, magnolol could inhibit spore germination and biofilm formation in a dose-dependent manner. Electron microscopy and membrane potential analysis indicated that the cytomembranes were disrupted, resulting in leakage of cellular contents. Transcriptomic profiling showed that magnolol treatment (1/2 × MIC) resulted in 585 differentially expressed genes (DEGs), including 295 down-regulated and 290 up-regulated genes. Bioinformatic analysis indicated that magnolol affected many potential cellular responses, including cellular metabolic process, locomotion, oxidative stress, and cell membranes. The pathway analysis revealed that DEGs mainly associated with flagellar assembly, bacterial chemotaxis, amino acids, and energy metabolism. Moreover, magnolol obviously reduced the amount of B. cereus in boiled rice and beef at 4 °C storage. These results provided insights into the molecular mechanism of magnolol against B. cereus and suggested that magnolol might be a promising natural antimicrobial agent for controlling the B. cereus in foods. Industrial relevanceBacillus cereus is considered as an important foodborne pathogenic microorganism that can exist as vegetative cells, spores, and biofilm in various food-processing environment, posing a big challenge for the food industry. Magnolol is a natural compound with potent antimicrobial activity against various pathogens and has been certified as safe by food safety organizations. Consequently, magnolol holds great promise as a natural antimicrobial agent for controlling B. cereus contaminations in foods.

Preparation and characterization of amidated pectin-gelatin-oxidized tannic acid hydrogel films supplemented with in-situ reduced silver nanoparticles for wound-dressing applications

Wound dressings play a crucial role in protecting injured tissues and promoting the healing process. Traditional fabrication of antibacterial wound dressings can be complex and may involve toxic components. In this study, we developed an innovative hydrogel film (AP:GE@OTA/Ag) composed of amidated pectin (AP), gelatin (GE), oxidized tannic acid (OTA) at varying concentrations, and in-situ reduced silver nanoparticles (AgNPs). FTIR and XRD analyses confirmed that crosslinking occurs via interactions between OTA quinone groups and free amino groups in AP and GE. TEM imaging demonstrated the well-dispersed AgNPs with an average particle size of 58.64 nm, while the TG measurements indicated the enhancement of the thermal stability compared to AP:GE films. The AP:GE@OTA/Ag films exhibited superior fluid uptake ability (90.96 % at 2 h), water retention capacity (91.69 % at 2 h), and water vapor transmission rate (1903.29 g/m2/day), alongside improved tensile strength (38 MPa). Additionally, these films showed excellent cytocompatibility and sustained potent antimicrobial activity against S. aureus and E. coli with low AgNPs loadings of 1.02 ± 0.13 μg/cm2. NIT-1 mouse insulinoma cells demonstrated robust proliferation when cultured with the prepared dressings. These films significantly accelerated wound repair in a skin excision model, indicating their potential clinical applications for wound healing.

Vitis heyneana extract mediated synthesis of silver nanoparticles with high bioactive and colorimetric sensing properties

The green synthesis of inorganic nanoparticles using plant extracts has been an important strategy to mitigate the uses of hazardous chemicals and thus reduce toxic by-products. We herein report for the first time the synthesis of silver nanoparticles (AgNPs) utilizing Vitis heyneana fruit peel as a key agent. Specifically, oleanolic acid was found in the extract and its crucial role as both reducing and stabilizing agent was experimentally evidenced. The as-synthesized AgNPs were morphologically and structurally characterized to possess quasi-spherical shapes with an average diameter of 11 nm and exhibit polycrystalline nature. Bioactive studies indicated that as-synthesized AgNPs revealed potent antimicrobial activities against Lactobaccillus plantarum, Pseudomonas aeruginosa, and Aspergillus flavus, demonstrating an IC50 value of 20.00 ± 2.05 μg ml−1 and a MIC value of 32 ± 0.03 μg ml−1 (against Pseudomonas aeruginosa); the NPs also possessed superior antioxidant activities with an IC50 value of 23.22 ± 1.25 μg ml−1 compared to vitamin C (18.23 ± 0.15 μg ml−1). The AgNPs further revealed capabilities of colorimetrically detecting Hg2+ ions with a limit of detection of 0.048 μM and a limit of quantitation of 0.16 μM. These findings therefore suggest promising uses of the phytosynthesized AgNPs in nanomedicine and sensing technology.

Preclinical evaluation of the individualized approach for chronic non-healing wounds management

Chronic non‑healing wounds (CNHW) are very common and often incorrectly treated, the morbidity and associated costs of chronic wounds management highlight the need to implement wound prevention and treatment concepts. Objective — to evaluate the possibility of different metal nanooxide polymer nanofilms use for CNHW’ local treatment. Materials and methods. The study design is based on evaluation of various types of dressing materials considering their option for use in CNHW local treatment. Samples of biodegradable polymer films (with an optimal composition of gelatin, polyvinyl alcohol, lactic acid, glycerin and distilled water) saturated with nanoparticles of several oxides with expected antibacterial and pro‑regenerative feature — nZnO, nMgO in concentrations of 1%, 5%, and 10% were used in the study of antimicrobial action and substance release profiling. Quarterly ammonium antiseptic decamethoxin 0.02% was used for control. Results. Obtained data shows that polymer based biodegradable films incorporating optimal component composition (gelatin, polyvinyl alcohol, lactic acid and glycerin) enriched with 5% and 10% zinc nanooxide have potent antimicrobial activity against both gram‑positive and gram‑negative microorganisms, the most common causative agents of CNHW’s. The ion release capacity analysis showed that the Zinc impregnated wound‑healing biodegradable polymer film gradually releases the active substance in a time dependent manner, and the nano‑sized particles of nanoZinc oxide are released from the polymer composition faster than ordinary zinc oxide. Conclusions. Complex natural biodegradable polymer based nanofilms are composite materials impregnated with metal nanooxides showing high potential in local treatment of chronic non‑healing wounds. Polymer film with 5% nanoZnO showed up to the 58% higher antimicrobial activity, comparable or exceeding the one of quarterly ammonium compound decamethoxin. Furthermore, nanoZnO impregnated polymer films compared to standard ZnO impregnated polymer films showed up to 63.2% faster substance release profile with rapid and more unified curve.

Synthesis of Novel 2-Quinolone linked 1,2,3-Triazole Derivatives as Potent Antimicrobial Activities: in silico Docking Studies

Synthesis of Novel 2-Quinolone linked 1,2,3-Triazole Derivatives as Potent Antimicrobial Activities: in silico Docking Studies

VG111: A novel formulation demonstrating clinical evidence of anti-pathogenic activity and accelerated wound healing in humans and companion animals

Objectives: The increasing incidence of chronic wounds such as diabetic foot ulcers and pressure ulcers, often compounded by bacterial infections and biofilm formation, presents significant challenges in wound management. Despite advancements in wound care products and a better understanding of molecular wound repair mechanisms, the treatment of chronic ulcerating conditions remains incomplete. VG111, a novel natural product formulation, emerges as a promising therapeutic candidate addressing the need for an effective wound healing agent with antimicrobial and tissue regenerative properties. Materials and Methods: A thorough evaluation of VG111 included antimicrobial assays to determine its minimum inhibitory concentration against an array of pathogens, assessment of its biofilm disruption capabilities, investigation into its profibrogenic activity through scratch assays, and analysis of its immunomodulatory effects on macrophage-derived cytokines. Quality consistency was ensured by high-performance liquid chromatography fingerprinting, while clinical applicability was assessed through observations in canine and human wound healing cases. Statistical Analysis: The cytotoxic effects of VG111 were assessed using a Two-way ANOVA, indicating no significant cytotoxicity at the tested concentration (Column factor p<0.0001). Results: VG111 demonstrated potent antimicrobial action with effective concentrations ranging from 2.5% to 5.0% v/v, targeting resistant strains of Methicillin-resistant Staphylococcus aureus, colistin-resistant Escherichia coli, Acinetobacter baumannii, and other priority pathogens. It showed biofilm clearance, enhanced fibroblast migration, and a favorable immunomodulatory profile by reducing inflammatory cytokines in vitro. In vivo applications corroborated these findings, with significant wound healing observed in both veterinary and clinical settings, negating the need for additional antibiotics. Conclusions: The study emphasized on VG111 as a robust wound healing agent with significant antimicrobial and biofilm-disrupting properties. Its broad-spectrum efficacy against critical pathogens and ability to promote tissue regeneration mark it as a promising avenue in the management of complex chronic wounds, meriting further clinical exploration.

Antibacterial, Antifungal, and Cytotoxic Potential of PlumbaginLoaded pH-Responsive Vaginal Nanoformulations.

Plumbagin is a naphthoquinone from the roots of the Plumbago species and exhibits anticancer activity. Translational usage of plumbagin in biomedical sciences is restricted due to its poor solubility and bioavailability. Therefore, pH-responsive plumbagin-loaded vaginal nanoformulations with polylactic acid (PLA)-chitosan polymeric coat were fabricated by inotropic gelation technique. Among the four (F1, F2, F3, F4) nanoformulations prepared, F3 exhibited good interaction of polymers with plumbagin as evidenced by FTIR, XRD, and thermal analysis. The positive zeta potential (48.4 ± 5.57mV), optimal size (694 ± 65.76nm), low PDI (0.157), and good encapsulation efficiency (77.8 ± 3.62%) of F3 were significant. The indirect method of drug loading (58.35 ± 5.00%) confirmed the drug content of about 495.44 ± 5.00µg of plumbagin in 1mg of F3. The drug loading pattern was confirmed by TEM analysis, and the spherical morphology of the nanocomposite was confirmed by SEM analysis. F3 formulation showed 46% and 25.2% of drug release in 24h in simulated vaginal fluid at pH 4.5 and 7 respectively with sustained release and hydrolyses of lactic acid from PLA. Among all the nanoformulations evaluated, nanoformulation F3 with promising physicochemical properties showed good antifungal and antibacterial activity against various fungal and bacterial strains. F3 exhibited potent cytotoxicity with an IC50 of 3.6 ± 0.12µg/ml for HeLa and an IC50 of 0.81 ± 0.01µg/ml for SiHa cells. Altogether, the nanoformulation F3 exhibited potent antimicrobial activity against vaginal infections and cytotoxicity against cervical cancer cell lines.

Lactobacillus-isolated exopolysaccharide as emulsifier ensure extended stability of eugenol encapsulation, potent anti-microbial activity, and application on fresh produce

In this study, we employed a novel encapsulation approach to develop a stable eugenol oil-in-water (O/W) emulsion by using Lactobacillus plantarum ATCC 8014 isolated exopolysaccharide (EPS) as a natural emulsifier. The emulsion was optimized and analyzed for physical stability, microstructure, rheology, and chemical behavior using fourier-transform infrared analysis (FTIR). The eugenol emulsion consisting of a 40:60 O/W ratio with 3 % w/v EPS exhibited a desired droplet size of 192 ± 1.89 nm with multimodal size distribution, polydispersity index of 0.362 ± 0.01 and zeta-potential of −32 ± 1.90 mV. Scanning electron microscopy (SEM) revealed porous and granulated structures with profound consistency. EPS maintained its emulsifying activity across processing conditions (−20 to 70 °C, pH 3–9, salinity 1 %–30 %), with stability over 90 days. Both EPS and eugenol synergistically enhanced the antimicrobial activity of emulsion against Listeria monocytogenes B600 and Salmonella Poona 36. The practical application of optimized emulsion was assessed by demonstrating a reduction in microbial load on the lettuce surface. Microbial load was determined by immersion and sprayed treatment methods which resulted in more than 3.0 log reduction. This potential application of lactobacillus–derived EPS as a natural emulsifier for encapsulating bioactive essential oils will enable its future applications for food safety.

Green Synthesis of Chitosan-Coated Silver Nanoparticles (Ch-AgNPs): Harnessing Nature for Sustainable and Safe Nanomaterial Production

The production of silver nanoparticles (AgNPs) using green synthesis methods promotes the use of environmentally friendly materials and facilitates a more sustainable production process by reducing environmental impact. In addition, combining the metal nanoparticles with biopolymers are getting important to enhance the safety profiles of formulations to determine the biological activities. With this concept, AgNPs were synthesized by green synthesis method from Betula spp. tree branches as reported previously by us and in current study, synthesized AgNPs were coated by one of biopolymer. Herein, Chitosan was used as capping and stabilizing agent. Characterization of the biosynthesized silver nanoparticles (AgNPs) and Chitosan coated silver nanoparticles (Ch-AgNPs) were evaluated with various techniques. Through this analysis, it was elucidated that the phenolic compounds present in Betula extract and Chitosan played dual roles as both reducing and capping agents, facilitating the formation of Ch-AgNPs. Particular size analysis by dynamic light scattering (DLS) and scanning electron microscopy (SEM) indicated that the Ch-AgNPs ranged from 49 to 118 nm in size, with a narrow size distribution. X-Ray Differentiation (XRD) patterns confirmed the high crystallinity of the resulting particles. Fourier transform infrared (FTIR) analysis further supported these findings, revealing the involvement of phenolic compound extracts in both the formation and stabilization of AgNPs. Additionally, FTIR confirmed the surface modification of AgNPs by chitosan. The efficiency of surface modified Ch-AgNPs was compared with uncoated AgNPs for their antimicrobial activity, antiproliferative efficiency and biocompatibility. Cell culture studies demonstrated that AgNPs were less toxic to L929 cells while maintaining effective cytotoxicity against HT-29 cells. Moreover, surface modification with chitosan enhanced the toxicity of AgNPs against HT-29 cells Furthermore, the first synthesized and evaluated Ch-AgNPs with this study from Betula extract, exhibited potent antimicrobial activity against both Gram-positive and Gram-negative bacteria. Our findings indicate that novel synthesized Ch-AgNPs formula may present a biocompatible and safety approach for further anticancer and antimicrobial studies.

Monoterpenoid indole alkaloids from the stem barks of Voacanga africana and their chemotaxonomic significance

The phytochemical investigation of the stem barks of Voacanga africana resulted in the isolation of fifteen known monoterpenoid indole alkaloids (1–15). The structures of the alkaloids were determined by comparison of their physical and spectroscopic data with those reported in literature. Twelve of these metabolites (4–15) were previously unreported within the genus Voacanga, thus they can serve as chemotaxonomic markers for V. africana to differentiate between V. africana from other species of the genus Voacanga. The alkaloids 3-oxoconopharyngine (6), ervahainanmine (10), crassanine (14) and conolobine A (15) hold the potential to serve as chemical markers for distinguishing V. africana from other family species. Furthermore, compounds 3, 6, 10, 12 showed potential antimicrobial activities against Candida albicans and Bacillus subtilis with MIC values of 6.25–12.50 μg/mL.

New thiazole derivatives linked to pyridine, fused pyridine, pyrimidine and thiazolopyrimidine scaffolds with potential dual anticancer and antimicrobial activities: Design, synthesis and docking simulation

The present study involved the design and synthesis of a novel series of thiazole derivatives 3, 5, 7, 8, 10–13 having various heterocyclic scaffolds, including pyrazole, pyridine, and/or pyrimidine. Upon screening of their antiproliferative efficacy, pyrazolo[3,4-b]pyridine 5a,b and pyrimidine 10a,b, afforded excellent activity against cancerous HepG-2 and MCF-7 cell lines with safety borders against normal human diploid cell line WI-38 comparing with doxorubicin and erlotinib. Then, their impact upon the apoptotic indicators; caspase-3, Bax and Bcl-2 was assessed. Regarding to antimicrobial activities, all screened Gram-positive and Gram-negative bacteria and fungal strains except Candida albicans, were effectively inhibited by the thiazole moiety bearing pyrazolo[3,4-b]pyridine 5a,b and pyrimidine 10a,b. Additionally, thiazole-pyrazolo[3,4-b]pyridine 5b exhibited remarkable and superior inhibitory properties against EGFR and E. coli DNA gyrase (IC50 = 0.3‏5 ± 0.‏25 and ‏‏2‏‏‏.55‏ ± 0.03 µM, respectively) in comparison with references erlotinib and novobiocin (IC50 = 0.27 ± 0.02 and 3.78 ± 0.02 µM, respectively). In order to provide improved optimization and rationalization of effective novel anticancer and antimicrobial leads, in silico ADMET and docking investigations were ultimately constructed.

Synthesis and Photophysical Characterization of Fluorescent Naphtho[2,3-d]thiazole-4,9-Diones and Their Antimicrobial Activity against Staphylococcus Strains.

The chemical reaction of 2-(methylsulfinyl)naphtho[2,3-d]thiazole-4,9-dione (3) using different amines, including benzylamine (4a), morpholine (4b), thiomorpholine (4c), piperidine (4d), and 4-methylpiperazine (4e), produced corresponding new tricyclic naphtho[2,3-d]thiazole-4,9-dione compounds (5a-e) in moderate-to-good yields. The photophysical properties and antimicrobial activities of these compounds (5a-e) were then characterized. Owing to the extended π-conjugated system of naphtho[2,3-d]thiazole-4,9-dione skeleton and substituent effect, 5a-e showed fluorescence both in solution and in the solid state. The introduction of nitrogen-containing heterocycles at position 2 of the thiazole ring on naphtho[2,3-d]thiazole-4,9-dione led to large bathochromic shifts in solution, and 5b-e exhibited orange-red fluorescence with emission maxima of over 600 nm in highly polar solvents. Staphylococcus aureus (S. aureus) is a highly pathogenic bacterium, and infection with its antimicrobial-resistant pathogen methicillin-resistant S. aureus (MRSA) results in serious clinical problems. In this study, we also investigated the antimicrobial activities of 5a-e against S. aureus, MRSA, and S. epidermidis. Compounds 5c with thiomorpholine group and 5e with 4-methylpiperazine group showed potent antimicrobial activity against these bacteria. These results will lead to the development of new fluorescent dyes with antimicrobial activity in the future.

Insights into the Chemistry, Structure, and Biological Activity of Human Salivary MUC7 Fragments and Their Cu(II) and Zn(II) Complexes.

Mucin 7 (MUC7) is one of the salivary proteins whose role in the innate immune system is widely known, but still, neither its mechanism of action nor the impact of its metal coordination is fully understood. MUC7 and its fragments demonstrate potent antimicrobial activity, serving as a natural defense mechanism for organisms against pathogens. This study delves into the bioinorganic chemistry of MUC7 fragments (L1─EGRERDHELRHRRHHHQSPK; L2─EGRERDHELRHRR; L3─HHHQSPK) and their complexes with Cu(II) and Zn(II) ions. The antimicrobial characteristics of the investigated peptides and their complexes were systematically assessed against bacterial and fungal strains at pH 5.40 and pH 7.40. Our findings highlight the efficacy of these systems against Streptococcus sanguinis, a common oral cavity pathogen. Most interestingly, Zn(II) coordination increased (or triggered) the MUC7 antimicrobial activity, which underscores the pivotal role of metal ion coordination in governing the antimicrobial activity of human salivary MUC7 fragments against S. sanguinis.

A 14-amino acid cationic peptide Bolespleenin334-347 from the marine fish mudskipper Boleophthalmus pectinirostris exhibiting potent antimicrobial activity and therapeutic potential

Antimicrobial peptides (AMPs) are an important component of innate immunity in both vertebrates and invertebrates, and some of the unique characteristics of AMPs are usually associated with their living environment. The marine fish, mudskipper Boleophthalmus pectinirostris, usually live amphibiously in intertidal environments that are quite different from other fish species, which would be an exceptional source of new AMPs. In the study, an AMP named Bolespleenin334-347 was identified, which was a truncated peptide derived from a new functional gene found in B. pectinirostris, that was up-regulated in response to bacterial challenge. Bolespleenin334-347 had only 14 amino acid residues, including five consecutive arginine residues. It was found that the peptide had broad-spectrum antibacterial activity, good thermal stability and sodium ion tolerance. Bolespleenin334-347 killed Acinetobacter baumannii and Staphylococcus aureus by disrupting the structural integrity of the bacterial membrane, leading to leakage of the cellular contents, and inducing accumulation of bacterial endogenous reactive oxygen species (ROS). In addition, Bolespleenin334-347 effectively inhibited biofilm formation of A. baumannii and S. aureus and long-term treatment did not lead to the development of resistance. Importantly, Bolespleenin334-347 maintained stable activity against clinically multi-drug resistant bacterial strains. In addition, it was noteworthy that Bolespleenin334-347 showed superior efficacy to LL-37 and vancomycin in a constructed mouse model of MRSA-induced superficial skin infections, as evidenced by a significant reduction in bacterial load and more favorable wound healing. This study provides an effective antimicrobial agent for topical skin infections with potential therapeutic efficacy for infections with drug-resistant bacteria, including MRSA.

Bioinspired ferromagnetic NiFe2O4 nanoparticles: Eradication of fungal and drug-resistant bacterial pathogens and their established biofilm

Nickel ferrite nanoparticles (NiFe2O4 NPs) were synthesized using the medicinally important plant Aloe vera leaf extract, and their structural, morphological, and magnetic properties were characterized by x-ray diffraction (XRD), fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy dispersive x-ray (EDX), and vibrating sample magnetometer (VSM). The synthesized NPs were soft ferromagnetic and spinel in nature, with an average particle size of 22.2 nm. To the best of our understanding, this is the first comprehensive investigation into the antibacterial, anticandidal, antibiofilm, and antihyphal properties of NiFe2O4 NPs against C. albicans as well as drug-resistant gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative multidrug resistant Pseudomonas aeruginosa (MDR-P. aeruginosa) bacteria. NiFe2O4 NPs showed potent antimicrobial activity (MIC 1.6–2 mg/mL) against the test pathogens. NiFe2O4 NPs at 0.5 mg/mL suppressed biofilm formation by 49.5–53.1 % in test pathogens. The study found that the NPs not only prevent the formation of biofilm, but also eliminate existing mature biofilms by 50.5–75.79 % at 0.5 mg/mL, which was further validated by SEM. SEM examination revealed a reduction in the number of cells that form biofilms and adhere to the surface. Additionally, it considerably impeded the colonization and aggregation of the biofilm strains on the glass surface. Light microscopic examination demonstrated that NPs effectively prevent the expansion of hyphae, filaments, and yeast-to-hyphae transformation in C. albicans, resulting in a substantial decrease in their ability to cause infection. Moreover, SEM images of the treated cells exhibited the presence of wrinkles, deformities, and impaired cell walls, which suggests an alteration and instability of the membrane. This study demonstrated the efficacy of the greenly manufactured NPs in suppressing the proliferation of candida, drug-resistant bacteria, and their preexisting biofilms, as well as yeast-to-hyphae transformation. Therefore, these NPs with broad spectrum applications could be utilized in health settings to mitigate biofilm-related health conditions caused by pathogenic microbial strains.

One-pot approach biosynthesis of nisin-conjugated zinc oxide nanoparticles using Bacillus subtilis ZBP4 with improved antibacterial activity

AbstractBiosynthesis of nisin-conjugated zinc oxide nanoparticles (N-ZnONPs) using the supernatant of Bacillus subtilis ZBP4 was demonstrated using a single-step reaction. Various amounts of nisin (5, 10, 15 mg/mL) and 8 mM ZnSO4.7H2O were reacted in the cell-free supernatant of Bacillus subtilis ZBP4 at 33 °C for 48 h. Surface plasmon resonance peaks created by N-ZnONPs were measured at 341–342 nm with a UV-VIS spectrophotometer, and the band-gap energy was calculated as 3.38 eV, indicating the nano-conjugates acted as semiconductors. Transmission electron microscopy (TEM) images showed that the N-ZnONPs were pseudo-spherical with an average diameter of 23 nm. Fourier transform infrared (FTIR) spectra analysis confirmed the presence of nisin as well as other organic substances in the structure. N-ZnONPs had potent antimicrobial activity on Escherichia coli O157:H7 and Staphylococcus aureus; the minimum inhibition concentrations were 0.05 and 1 mg/mL, respectively. In addition, conjugation with nisin increased the long-term stability of nanoparticles when compared to unconjugated ZnONPs.

Structure–activity relationships of the intramolecular disulphide bonds in LEAP2, an antimicrobial peptide from Acrossocheilus fasciatus

BackgroundThe liver-expressed antimicrobial peptide 2 (LEAP2) plays a pivotal role in the host’s immune response against pathogenic microorganisms. Numerous such antimicrobial peptides have recently been shown to mitigate infection risk in fish, and studying those harboured by the economically important fish Acrossocheilus fasciatus is imperative for enhancing its immune responses against pathogenic microorganisms. In this study, we cloned and sequenced LEAP2 cDNA from A. fasciatus to examine its expression in immune tissues and investigate the structure–activity relationships of its intramolecular disulphide bonds.ResultsThe predicted amino acid sequence of A. fasciatus LEAP2 was found to include a signal peptide, pro-domain, and mature peptide. Sequence analysis indicated that A. fasciatus LEAP2 is a member of the fish LEAP2A cluster and is closely related to Cyprinus carpio LEAP2A. A. fasciatus LEAP2 transcripts were expressed in various tissues, with the head kidney exhibiting the highest mRNA levels. Upon exposure to Aeromonas hydrophila infection, LEAP2 expression was significantly upregulated in the liver, head kidney, and spleen. A mature peptide of A. fasciatus LEAP2, consisting of two disulphide bonds (Af-LEAP2-cys), and a linear form of the LEAP2 mature peptide (Af-LEAP2) were chemically synthesised. The circular dichroism spectroscopy result shows differences between the secondary structures of Af-LEAP2 and Af-LEAP2-cys, with a lower proportion of alpha helix and a higher proportion of random coil in Af-LEAP2. Af-LEAP2 exhibited potent antimicrobial activity against most tested bacteria, including Acinetobacter guillouiae, Pseudomonas aeruginosa, Staphylococcus saprophyticus, and Staphylococcus warneri. In contrast, Af-LEAP2-cys demonstrated weak or no antibacterial activity against the tested bacteria. Af-LEAP2 had a disruptive effect on bacterial cell membrane integrity, whereas Af-LEAP2-cys did not exhibit this effect. Additionally, neither Af-LEAP2 nor Af-LEAP2-cys displayed any observable ability to hydrolyse the genomic DNA of P. aeruginosa.ConclusionsOur study provides clear evidence that linear LEAP2 exhibits better antibacterial activity than oxidised LEAP2, thereby confirming, for the first time, this phenomenon in fish.

QSAR Reveals Decreased Lipophilicity of Polar Residues Determines the Selectivity of Antimicrobial Peptide Activity.

Antimicrobial resistance has increased rapidly, causing daunting morbidity and mortality rates worldwide. Antimicrobial peptides (AMPs) have emerged as promising alternatives to traditional antibiotics due to their broad range of targets and low tendency to elicit resistance. However, potent antimicrobial activity is often accompanied by excessive cytotoxicity toward host cells, leading to a halt in AMP therapeutic development. Here, we present multivariate analyses that correlate 28 peptide properties to the activity and toxicity of 46 diverse African-derived AMPs and identify the negative lipophilicity of polar residues as an essential physiochemical property for selective antimicrobial activity. Twenty-seven active AMPs are identified, of which the majority are of scorpion or frog origin. Of these, thirteen are novel with no previously reported activities. Principal component analysis and quantitative structure-activity relationships (QSAR) reveal that overall hydrophobicity, lipophilicity, and residue side chain surface area affect the antimicrobial and cytotoxic activity of an AMP. This has been well documented previously, but the present QSAR analysis additionally reveals that a decrease in the lipophilicity, contributed by those amino acids classified as polar, confers selectivity for a peptide to pathogen over mammalian cells. Furthermore, an increase in overall peptide charge aids selectivity toward Gram-negative bacteria and fungi, while selectivity toward Gram-positive bacteria is obtained through an increased number of small lipophilic residues. Finally, a conservative increase in peptide size in terms of sequence length and molecular weight also contributes to improved activity without affecting toxicity. Our findings suggest a novel approach for the rational design or modification of existing AMPs to increase pathogen selectivity and enhance therapeutic potential.

Assessment of the Anticancer, Antimicrobial, and Antioxidant Activities of the Peganum harmala L. Plant

Introduction Synthetic chemical drug treatments have drawbacks including adverse effects and toxicity. Natural alternatives are sought after. Chemotherapy can be toxic. Medicinal plants offer a suggested alternative. This study examines P. harmala plant extracts for phenolic and flavonoid content, antimicrobial, antioxidant, and anticancer activities. Methods Two samples of P. harmala plant extract were prepared using ultrasonication, with ethanol concentrations of 100% and 50%. The total phenolic and flavonoid contents were determined using a chemical assay method. The antimicrobial activity of the extracts was evaluated against gram-positive bacteria ( Staphylococcus aureus and Streptococcus) and gram-negative bacteria ( Escherichia coli) using the diffusion procedure. The antioxidant impact of the extracts was assessed using the DPPH procedure. P. harmala extracts showed inhibitory effects on MCF7 breast cancer and HT29 colon cancer cell lines. Results The results of the study indicated that the P. harmala plant extracts were rich in phenolic compounds (with total phenolic content of 215.8 ± 3.5 and 155.8 ± 2.9 mg gallic acid per g extract for 50% and 100% ethanol extracts, respectively) and flavonoids (with total flavonoids content of 112.1 ± 3.1 and 92.3 ± 1.8 mg catechin per g extract) and had a high rate of antioxidant activity. The 50% ethanol extract yielded 411.8 ± 3.5 μmol trolox/g, while the 100% ethanol extract yielded 312.9 ± 8.2 μmol trolox per g extract. P. harmala extracts exhibited potent antimicrobial activity against E. coli, S. aureus, and Streptococcus. They also demonstrated strong anticancer activity, causing significant cell death in breast and colon cancer cell lines within 48 h of culturing. Conclusion P. harmala ethanolic extracts are rich in polyphenolic compounds and flavonoids, displaying high antioxidant activity. They also exhibit strong inhibitory effects against gram-positive and gram-negative bacteria and demonstrate potent anticancer activity against breast and colon cancer cell lines.