Potent Antibacterial Activity Research Articles

Antimicrobial Peptide with a Bent Helix Motif Identified in Parasitic Flatworm Mesocestoides corti.

The urgent need for antibiotic alternatives has driven the search for antimicrobial peptides (AMPs) from many different sources, yet parasite-derived AMPs remain underexplored. In this study, three novel potential AMP precursors (mesco-1, -2 and -3) were identified in the parasitic flatworm Mesocestoides corti, via a genome-wide mining approach, and the most promising one, mesco-2, was synthesized and comprehensively characterized. It showed potent broad-spectrum antibacterial activity at submicromolar range against E. coli and K. pneumoniae and low micromolar activity against A. baumannii, P. aeruginosa and S. aureus. Mechanistic studies indicated a membrane-related mechanism of action, and circular dichroism spectroscopy confirmed that mesco-2 is unstructured in water but forms stable helical structures on contact with anionic model membranes, indicating strong interactions and helix stacking. It is, however, unaffected by neutral membranes, suggesting selective antimicrobial activity. Structure prediction combined with molecular dynamics simulations suggested that mesco-2 adopts an unusual bent helix conformation with the N-terminal sequence, when bound to anionic membranes, driven by a central GRGIGRG motif. This study highlights mesco-2 as a promising antibacterial agent and emphasizes the importance of structural motifs in modulating AMP function.

A silver lining in MRSA treatment: The synergistic action of poloxamer-stabilized silver nanoparticles and methicillin against antimicrobial resistance

BackgroundIncreasing antibiotic resistance in bacterial infections, including drug-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), necessitates innovative therapeutic solutions. Silver nanoparticles are promising for combating infections, but toxicity concerns emphasize the importance of factors like dosage, size, shape, and surface chemistry. Hence, exploring poloxamer as a stabilizing agent to reduce its toxicity and enhance the antibacterial effect on MRSA is investigated. MethodsSilver nanoparticles stabilized with poloxamer (AgNPs@Pol) were synthesized through the chemical reduction method and characterized using UV–visible spectrophotometer, HR-TEM, DLS, and Zeta potential measurements. Subsequently, the antibacterial activity of AgNPs@Pol alone and in combination with methicillin against MRSA and methicillin-susceptible S. aureus (MSSA) was evaluated using the broth microdilution method. ResultsAgNPs@Pol showed significant efficacy against MRSA and MSSA, achieving a 100 % reduction in colony-forming units (CFU) at 9.7 μg/ml. The minimum inhibitory concentration (MIC) against MRSA and MSSA was 8.6 μg/ml and 4.3 μg/ml, respectively. A synergistic effect was observed when AgNPs@Pol was combined with methicillin. Treatment with AgNPs@Pol increased reactive oxygen species (ROS) production in both strains, contributing to its antibacterial activity. Real-time qPCR analysis indicated the downregulation of genes involved in antimicrobial resistance and cell adhesion in both strains. Further, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated low cytotoxicity for AgNPs@Pol against MCF-7, MG-63, and NIH-3T3 cell lines. ConclusionThe developed AgNPs@Pol demonstrated extensive colloidal stability, potent antibacterial activity and synergistic effect with methicillin against MRSA and MSSA. Further studies in primary cells and in vivo models may validate its potential for clinical applications.

Local Delivery of Exosomes and Antibiotics in Hydroxyapatite-Based Nanocement for Osteomyelitis Management.

The management of bone and joint infections is a formidable challenge in orthopedics and poses a global health concern. While clinical management emphasizes infection prevention and complete eradication, an effective strategy for stabilizing skeletal tissue with adequate soft tissue coverage remains limited. In this study, we have employed a novel approach of using the local delivery of exosomes and antibiotics (rifampicin) using a hydroxyapatite-based nanocement carrier to manage the residual space created during debridement effectively. Additionally, we synthesized a periosteum-guiding antioxidant herbal membrane to leverage the inherent periosteum regeneration capability of the bone, facilitating bone callus repair and natural healing. The synthesized scaffolds were biocompatible and demonstrated potent antibacterial activity in vitro. When evaluated in vivo in the Staphylococcus aureus-induced rat tibial osteomyelitis model, the released drugs successfully cleared the residual bacteria and the released exosome promoted bone healing, resulting in 3-fold increase in bone volume as analyzed via micro-CT analysis. Immunofluorescence staining of periosteum-specific markers also indicated the complete formation of periosteal layers, thus highlighting the complete bone repair.

MMV 1804559 is a potential antistaphylococcal and antibiofilm agent targeting the clfA gene of Staphylococcus aureus.

Staphylococcus aureus, a high-priority pathogen proclaimed to cause infections ranging from mild to life-threatening, presents significant challenges in treatment. New therapies can be developed quicker using open drug discovery platforms offering a distinct approach to expedite the development of innovative antibacterial and anti-biofilm therapeutics. This study set out to address these issues by finding new uses for current medications to find compounds that are effective against S. aureus. In this study, we screened the global priority health box, launched by Medicines for Malaria Ventures containing 240 compounds, for their effectiveness against S. aureus. MMV1795508, MMV1542799, MMV027331, MMV1593278, and MMV1804559 showed potential antibacterial activity at 10µM concentration. These compounds underwent further evaluation for their ability to clear intracellular bacteria, disrupt biofilm formation and eradicate existing biofilms. MMV1804559 demonstrated strong efficacy across all tested parameters, achieving 94% inhibition of intracellular bacteria, 79.19% disruption of biofilm cells, and 66.18% inhibition of biofilm formation. Scanning electron microscopy revealed notable membrane perforations and blebbing in MMV1804559-treated cells, indicating its impact on bacterial membranes. Gene expression analysis of cells treated with MMV1804559 showed downregulation of clfA and clfB genes, critical for biofilm formation. Additionally, docking studies confirmed the binding affinity of MMV1804559 with clfA, supported by favorable docking scores, MM/GBSA binding energy, and increased hydrogen bond interactions in the binding pocket, suggesting clfA as a target for MMV1804559. MMV1804559 could serve as a potential therapy for S. aureus by targeting biofilm development and cell adhesion processes.

Copper oxide/biopolymer nanocomposites: synthesis and applications, a comprehensive review

Copper oxide particles have a significant role in various fields due to their many properties like special shape, size, and high surface area. Due to their rarity and unique characteristics, such as their large surface area, paramagnetic nature, and ease of separation, Copper oxide nanoparticles have received the greatest attention. Chitosan, Guar Gum, Tamarind, Alginate, starch, cellulose, polysaccharide, etc. are examples of natural biopolymers that have proven to be excellent hosts for the creation of CuO nanoparticles. Long-established fabrication techniques for biopolymer-based CuO nanocomposites include co-precipitations, green synthesis, Solvent Casting Method, Alco thermal method, and Sol-Gel methods. Excellent biological characteristics of Copper oxide/biopolymer nanocomposites include their potent antibacterial activity against a variety of diseases as well as bacteria that are resistant to antibiotics. These characteristics have sparked the creation of numerous strategies with direct biological applications, including customized surfaces with antimicrobial effects, wound dressings, and modified textiles. This study aims to provide the very first biopolymer CuO nanoparticles to be reported in the previous ten years as well as its appealing methodology in diverse applications.

Statistical Design and Analysis for Enhanced Production of Tetracycline‐Conjugated Copper Oxide Nanoparticles with Improved Antimicrobial Properties

AbstractPurpose: Since decades, numerous antibiotics have been used to treat different bacterial illnesses; among these, tetracycline is one of the commonly used antibiotics, which has led to development of bacterial resistance. To tackle this critical issue, we have developed a novel, biocompatible nanodrug that improves the antibacterial activity of tetracycline by conjugating it with copper oxide nanoparticles, thereby addressing the problem of multidrug resistance in bacteria. Methods: In this study, using unipot approach, tetracycline conjugated copper oxide nanoparticles were synthesized where tetracycline act as reducing as well as stabilizing agent. These nanoparticles were characterized by different analytical and microscopic technique. For statistical analysis, FFD and CCD model were employed to assess the effect of various parameters (concentration, pH, temperature and time). Results: The synthesis of nanoparticles was confirmed through different techniques. Synthesized nanoparticles exhibited the highest antibacterial activity against various microbes including multi‐drug resistant microbes compared to its individual constituents. DPPH and ABTS assays revealed high antioxidant activity of nanoparticles whereas, biocompatibility was assessed via MTT assay. The drug release profile confirms the sustained release of tetracycline molecules. Conclusions: We have successfully developed tetracycline conjugated copper oxide nanoparticles exhibiting potent antibacterial, antioxidant and biocompatible activity.

Thiazoplanomicin, a new thiazolyl peptide antibiotic from the leaf-litter actinomycete Actinoplanes sp. MM794L-181F6.

A new bioactive substance was identified from a leaf-litter actinomycete strain by screening for antibacterial activity against Neisseria gonorrhoeae. The thiazolyl peptide antibiotic, named thiazoplanomicin, was isolated from the secondary metabolites of the leaf-litter actinomycetes Actinoplanes sp. MM794L-181F6 by extraction with n-butanol, silica gel column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Thiazoplanomicin was characterized by LC-HR-ESI-MS, NMR, and X-ray analyses, along with analysis of the degradation products and chemical derivatives, and determined to be a nocathiacin-like multiple macrocyclic thiazolyl peptide. Thiazoplanomicin showed potent antimicrobial activity against gonococcal strains, including those resistant to known anti-gonococcal compounds such as telithromycin, azithromycin, and ceftriaxone, with MIC values ranging from 0.0312 to 0.125 µg ml-1. Such anti-gonococcal activity has not been reported on nocathiacin-like thiazolyl peptide antibiotic so far. Similar to other thiazolyl peptide antibiotics, thiazoplanomicin also showed potent antibacterial activity against Gram-positive bacteria with MIC values ranging from 0.0005 to 0.0156 µg ml-1 but showed no antibacterial activity against Escherichia coli.

Investigation of antibacterial and anticancer activities of biosynthesized metal-doped and undoped zinc oxide nanoparticles.

Over the past 10 years, nanotechnology has emerged as a very promising technique for a wide range of biomedical applications. Green synthesized metal and metal oxide nanoparticles (NPs) are cheap, easy to produce in large quantities, and safe for the environment. Currently, efforts are being made to dope ZnO in order to improve its optical, electrical, and ferromagnetic qualities as well as its crystallographic quality. Actually, doping is one of the simplest methods for enhancing an NP's physicochemical characteristics because it involves introducing impure ions into the crystal lattice of the particle. In this study, the biosynthesis of zinc oxide NPs (ZnONPs) and metal-doped (Mg2+ and Ag+) ZnONPs was carried out by using aqueous and water-alcoholic extracts of Cynara scolymus L. leaves, Carthamus tinctorius L. flowers, and Rheum ribes L. (RrL) plant, which are rich in phytochemical content. Plant extracts act as a natural reducing, capping, and stabilizing agent in the production. The produced NPs were characterized using a variety of methods, such as ultraviolet-visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM). The produced metal-doped and undoped ZnONPs exhibited characteristic absorption peaks between 365 and 383nm due to their surface plasmon resonance bands. SEM analysis revealed that the NPs were oval, nearly spherical, and spherical. In the FTIR spectra, the Zn-O bonding peak ranges from 400 to 700cm-1. The peaks obtained in the range of 407-562cm-1 clearly represent the Zn-O bond. In addition, the FTIR results showed that there were notable amounts of phenol and flavonoid compounds in both the prepared extract and ZnONPs. According to DLS analysis results, the size distribution of produced NPs is between 120 and 786nm. The antibacterial properties of green produced NPs on Gram-positive (Staphylococcus aureus RN4220) and Gram-negative (Escherichia coli DH10B) bacterial strains were investigated by agar well diffusion method. In studies investigating the anticancer activities of biosynthesized NPs, mouse fibroblast cells (L929) were used as healthy cells and human cervical cancer cells (HeLa) were used as cancer cells. Only the produced Ag-ZnONPs showed potent dose-dependent antibacterial activity (at concentrations higher than 100µg/mL) against Gram-positive and Gram-negative bacteria. RrL-ZnONP-600 and RrL-ZnONP-800 NPs produced with water-ethanol extract of RrL plant and calcined at 600 and 800°C were effective at high concentrations in healthy cells and at low concentrations in HeLa cancer cells, showing that they have the potential to be anticancer agents. The study's findings highlight the potential of green synthesis techniques in the production of medicinal nanomaterials for the treatment of cancer and other biological uses.

Dodecanoyl-L-tryptophan: A Novel Natural Antibiotic Isolated from Mesophotic Sponge-associated Salinicola sp. LHM and its Biological Function

Background: Sponge-associated microbiota plays a crucial role in maintaining host health by providing chemical defense through the synthesis of diverse secondary metabolites. However, research on these secondary metabolites is still in its early stages. Objective: The present study aimed to investigate new natural antibiotics from mesophotic sponge symbiotic microbiota and explore its in vitro antibacterial activity and preliminary biological function. Methods: Bacteria strain Salinicola sp. LHM was isolated from sponge L. birotulata L26 and identified based on the 16S rRNA gene analysis. Subsequently, the strain was fermented using a liquid M9 medium and screened for antibiotics with an antibacterial guiding assay. Extensive chromatographic methods were introduced to isolate the target compound, and its chemical structure was elucidated by spectroscopic analysis (LC-MS, NMR). The minimum inhibitory concentration (MIC) and cytotoxicity experiments evaluated the isolated compound's biological activity. Furthermore, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quartz crystal microbalance with dissipation (QCM-D) were used to study the bactericidal mechanism of DLT. Finally, the preliminary biological function was explored by performing the cell-feeding experiment. Results: We successfully identified one novel natural antibiotic, dodecanoyl-L-tryptophan (DLT), in Salinicola sp. LHM isolated from mesophotic sponge Lotrochota birotulata L26. DLT exhibited potent antibacterial activity against the Bacillus subtilis and Staphylococcus aureus, with MIC values of 32 μM and 16 μM, respectively. The bactericidal tests showed that DLT broke the cell membrane to cause cell death by leaking the cell's inner content. Furthermore, the cell-feeding experiment proved that DLT producer- Salinicola sp. LHM could feed on the inner content of death cells. In addition, DLT also exhibited cytotoxicity against bronchial epithelial cells BEAS-2B, with an EC50 value of 150 μM, indicating a favorable selectivity profile. result: We successfully identified one novel natural antibiotic, dodecanoyl-L-tryptophan (DLT), in Salinicola sp. LHM isolated from mesophotic sponge Lotrochota birotulata L26. DLT exhibited potent antibacterial activity against the Bacillus subtilis and Staphylococcus aureus, with MIC values of 32 μM and 16 μM, respectively. The bactericidal tests showed that DLT broke the cell membrane to cause cell death by leaking the cell's inner content. Furthermore, the cell-feeding experiment proved that DLT producer- Salinicola sp. LHM could feed on the inner content of death cells. In addition, DLT also exhibited cytotoxicity against bronchial epithelial cells BEAS-2B, with an EC50 value of 150 μM, indicating a favorable selectivity profile. Conclusion: This research identified one novel natural antibiotic DLT and provided initial insights into the chemical defense exerted by Salinicola sp. LHM with its secondary metabolite DLT.

Dual Antimicrobial Activity of HTCC and Its Nanoparticles: A Synergistic Approach for Antibacterial and Antiviral Applications Through Combined In Silico and In Vitro Studies.

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC), a quaternized chitosan derivative, has been shown to exhibit a broad spectrum of antimicrobial activity, especially against bacteria and enveloped viruses. Despite this, molecular docking studies showing its atomic-level mechanisms against these microorganisms are scarce. Here, for the first time, we employed molecular docking analyses to investigate the potential antibacterial activity of HTCC against Staphylococcus aureus and its antiviral activity against human immunodeficiency virus 1 (HIV-1). According to the findings, HTCC exhibited promising antibacterial activity with high binding affinities; however, it had limited antiviral activity. To validate these theoretical outcomes, experimental studies were conducted. Different derivatives of HTCC were synthesized and characterized using NMR, XRD, FTIR, and DLS. The in vitro assays validated the potent antibacterial efficacy of HTCC against S. aureus, whereas the antiviral studies did not show good antiviral activity. However, our research also revealed a promising avenue for further exploration of the antimicrobial activity of HTCC nanoparticles (NPs), since, thus far, no studies have been conducted to show the antiviral activity of HTCC NPs against HIV-1. The nanosized HTCC exhibited superior antiviral performance compared to the parent polymers, with complete (100%) inhibition of HIV-1 viral activity at the highest tested concentration (0.33 mg/mL).

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.

Niosome-loaded Tet-Amp against S. aureus, K. pneumoniae, and P. aeruginosa.

Biofilm-associated disorders contribute to elevated morbidity and death rates among patients. We propose synthesizing niosomal structures containing the antibiotics tetracycline and ampicillin ((Tet/Amp)-Nio) and investigating their impact on standard strains of S. aureus, K. pneumoniae, and P. aeruginosa. The antibacterial and anti-biofilm effects of synthesized niosomes against standard pathogenic bacterial strains were studied, and also its cytotoxic activity was investigated against human foreskin fibroblast (HFF) cell line. The optimal formulation (F2) had an average particle size of 196.90 ± 4.57nm, a PDI of 0.223 ± 0.013, a Zeta-potential of -19.25 ± 1.19 mV, a %EE of 70.92 ± 1.75% for Tet and 58.34 ± 1.85% for Amp, and a %Release rate of 49.34 ± 1.78% for Tet and 62.67 ± 1.19% for Amp. The release of Tet and Amp drugs over 48h was 47% and 61%, respectively, from the (Tet/Amp)-Nio formulation. Also, our findings demonstrated that the Tet/Amp)-Nio have potent antibacterial, anti-biofilm, and lower cytotoxic activity compared to the Tet + Amp. In addition, (Tet/Amp)-Nio can upregulate the expression level of matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) genes, which shows their great activity in the wound healing process. The findings of the current investigation suggest that (Tet/Amp)-Nio enhances its antibacterial and antibiofilm effects against S. aureus, P. aeruginosa, and K. pneumoniae isolates. These formulations may serve as a novel approach for targeted drug delivery.

Anticancer Effect of Cycas media: Molecular Basis Through Modulation of PI3K/AKT/mTOR Signaling Pathway.

Many researchers are focusing on screening the biological activities of plants owing to their safety and possible pharmacological actions. Consequently, we aimed to explore the antiproliferative and cytotoxic properties of Cycas media methanolic extract on HepG2 cell lines. Moreover, we also explore the antitumor action against the experimentally induced solid Ehrlich carcinoma (SEC) model and investigate the possible involved molecular mechanisms. Also, the antibacterial action of the extract was elucidated. Different concentrations of the extract were incubated with HepG2 to determine cytotoxicity, followed by cell cycle analysis. The in vivo experiment was accomplished by grouping the animals into four different groups (n = 10); normal control, SEC, C. media 100, and C. media 200. The extract was administered at 100 and 200 mg/kg. Tumor volume, tumor inhibition rate, toxicity profile, and antioxidant biomarkers were determined. Moreover, the PI3K/AKT/mTOR signaling pathway was investigated as a possible underlying antitumor mechanism. The tumor control group showed a remarkable upregulation for PI3K, p-AKT, and p-mTOR, along with downregulation for the antioxidant SOD and GPX4, as well as decreased levels of GSH and MDA. C. media extract reversed these parameters to a significant level and the higher dose showed a superior antitumor effect. C. media extract showed antiproliferative effects against HepG2 cells, along with a suppressive action on the PI3K/AKT/mTOR pathway and an antioxidant effect. Additionally, C. media had antibacterial consequences against S. aureus isolates with minimum inhibitory concentrations from 32 to 128 µg/mL. It also caused a noteworthy growth delay as well as a notable reduction in the membrane integrity of S. aureus isolates. These beneficial outcomes suggest C. media to have potential antitumor and antibacterial activities.

In-vitro and in-silico studies based discovery of 2-aryl-N-(4-morpholinophenyl)thiazol-4-amines as promising DNA gyrase inhibitors

Background: DNA gyrase is an important enzyme for the survival of bacteria. Many DNA gyrase inhibitors are in clinical practice. However, these inhibitors also encompass certain toxic and drug/food interactions. This warrants the development of a new template as DNA gyrase inhibitors. Therefore, this study aimed to deliver morpholine-based thiazoles (5a-5l) as safer DNA gyrase inhibitors.Methods: The 5a-5l were prepared by reacting compound 3 with various aryl thioamides. The structures of 5a-5l were ascertained by their spectral records. The 5a-5l were subjected to their antibacterial activity potential (serial plate dilution method), DNA gyrase inhibiting activity, and toxicity analysis (MTT assay) against HepG2 &amp; Vero cell lines. The in-silico studies (pharmacokinetic parameters and molecular docking) of 5a-5l were likewise performed.Results: It was surprisingly observed that the MIC values of 5a-5l were equal to the MIC values of ciprofloxacin (12.5 µg/ml) against the tested bacteria, whereas the DNA gyrase inhibitory activity (IC50 in µg/ml) of 5h (3.52), 5g (3.76), 5f (3.88), 5e (4.08), 5l (4.11), 5b (4.28), 5k (4.28), 5i (4.30), and 5d (4.32) was equal/better than ciprofloxacin (4.32). The MTT assay also implied the non-cytotoxic nature of 5a-5l against HepG2 &amp; Vero cell lines up to 200 µg/ml concentration. The docking outcomes indicated a similar binding pattern of 5a-5l and ciprofloxacin at the active site of DNA gyrase, wherein 5a-5l displayed a better binding affinity for the active site. The in-silico toxicity data employing the ProTox-II web server indicated no hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, or cytotoxic effect of 5a-5l. Also, the SwissADME software supported the drug-likeliness properties and high gastrointestinal absorption of 5a-5l.Conclusion: Compounds 5h, 5g, 5f, 5e, 5l, 5b, 5k, 5i, and 5d are potent DNA gyrase inhibitors with promising safety profiles.Keywords: Discovery; Morpholine; Thiazole; DNA gyrase; MTT assay; Docking

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.

Utilizing Ziziphus spina-christi for eco-friendly synthesis of silver nanoparticles: Antimicrobial activity and promising application in wound healing

Abstract Wound healing is a critical process essential for the body’s recovery from injuries, often complicated by bacterial infections. Silver nanoparticles (AgNPs) have gained attention due to their antibacterial and tissue-regenerative properties. However, conventional chemical synthesis methods for AgNPs pose environmental risks. This study utilizes Ziziphus spina-christi (ZSC) extract for the eco-friendly synthesis of AgNPs, evaluating their antibacterial and wound-healing capabilities. The AgNPs-ZSC showed an absorption maximum at λ max of 460 nm, a particle size of 111.2 ± 1.09 nm, a polydispersity index of 0.38 ± 0.006, and a zeta potential of −27.0 ± 0.231 mV. The synthesized AgNPs-ZSC were spherical, non-aggregated, and exhibited potent antibacterial activity superior to chloramphenicol. Furthermore, the AgNPs-ZSC cream significantly promoted wound closure, epithelial tissue proliferation, and granulation tissue formation in rats, showing no signs of toxicity or adverse reactions. In conclusion, AgNPs-ZSC cream demonstrates excellent antibacterial and wound-healing properties, presenting a sustainable alternative to conventional chemical methods for AgNP synthesis.

Synergy of bacteriophage depolymerase with host immunity rescues sepsis mice infected with hypervirulent Klebsiella pneumoniae of capsule type K2

ABSTRACT The hypervirulent Klebsiella pneumoniae (hvKp) with K1 and K2 capsular types causes liver abscess, pneumonia, sepsis, and invasive infections with high lethality. The presence of capsular polysaccharide (CPS) resists phagocytic engulfment and contributes to excessive inflammatory responses. Bacteriophage depolymerases can specifically target bacterial CPS, neutralizing its defense. Based on our previous research, we expressed and purified a bacteriophage depolymerase (Dep1979) targeting hvKp with capsule type K2. Interestingly, although Dep1979 lacked direct bactericidal activity in vitro, it exhibited potent antibacterial activity in vivo. Low-dose Dep1979 (0.1 mg/kg) improved the 7-day survival of immunocompetent mice to 100%. Even at 0.01 mg/kg, mice achieved 100% survival at 5 days, although efficacy sharply declined at doses as low as 0.001 mg/kg. Following Dep1979 treatment, reduced expression of inflammatory factors and no apparent tissue damage were observed. However, therapeutic efficacy significantly diminished in immunosuppressed mice. These findings underscore the critical role of Dep1979 in disarming CPS, which synergizes with host immunity to enhance antibacterial activity against hvKp.

The Comparison of Antibacterial Efficacy, Cell Proliferation, and Wound Healing Properties in Extracts Derived from Leaves and Inflorescences of Hang Kra Rog Phu Phan ST1 (Cannabis sativa L.)

The therapeutic potential of Cannabis sativa extracts in wound healing applications has garnered significant interest due to their diverse pharmacological properties. This study aimed to comparatively evaluate the antibacterial properties and wound-healing activity of ethanolic extracts derived from C. sativa leaves and inflorescences of the Hang Kra Rog Phu Phan ST1 cultivar. The extracts were prepared using ethanol, and their antibacterial properties, cytotoxicity and ability to promote cell proliferation and migration were investigated. The antibacterial activity was assessed against Staphylococcus epidermidis TISTR 518, Klebsiella pneumoniae TISTR 1383, Pseudomonas aeruginosa TISTR 2370, Staphylococcus aureus TISTR 1466 and Bacillus cereus TISTR 2373 using the disk diffusion method and broth microdilution assay. Cell viability and proliferation were evaluated using the MTT assay on human fibroblasts in serum-supplemented and serum-depleted media. The scratch wound healing assay was employed to quantify cell migration and wound closure. The results demonstrated that both leaf and inflorescence extracts exhibited antibacterial activity, with the inflorescence extract showing higher efficacy against S. aureus. Furthermore, the extracts enhanced fibroblast proliferation and migration in a concentration-dependent manner. Notably, the leaf extract outperformed the inflorescence extract in promoting fibroblast proliferation and migration, particularly at earlier time points. These findings suggest that C. sativa extracts, particularly from the leaves, possess wound-healing properties and could be developed as novel therapeutic agents for promoting efficient wound repair and managing chronic non-healing wounds. HIGHLIGHTS This research is the inaugural exploration into the antibacterial properties and wound healing capabilities of the Cannabis sativa L. Hang Kra Rog Phu Phan ST1 cultivar, a unique variant of Cannabis sativa. This strain has received official recognition and registration from the Rajamangala University of Technology Isan, Thailand. Our findings reveal that extracts derived from the leaves and inflorescences of the Hang Kra Rog Phu Phan ST1 strain display potent antibacterial activity against five tested pathogenic bacteria, namely Staphylococcus epidermidis TISTR 518, Klebsiella pneumoniae TISTR 1383, Pseudomonas aeruginosa TISTR 2370, Staphylococcus aureus TISTR 1466, and Bacillus cereus TISTR 2373. Moreover, these extracts stimulate the growth and movement of human fibroblasts. These compelling results underscore the potential for harnessing this plant as an efficacious agent for wound healing. GRAPHICAL ABSTRACT

Synthesis and characterization of silver nanoparticles and their promising antimicrobial effects

Silver nanoparticles have garnered significant interest due to their unique properties, such as small size, high specific surface area, and high reactivity, making them valuable in various industries, including medicine, healthcare, consumer products, and food. The synthesis of silver nanoparticles has been extensively studied, with numerous methods reported, including physical, chemical, and biological routes. These synthesis methods can influence the antibacterial properties of silver nanoparticles, which is critical in hospital settings where pathogen exposure and antibiotic resistance are prevalent concerns. Notably, hospital environments face high infection risks from pathogens like Staphylococcus aureus and Pseudomonas aeruginosa, necessitating new antibacterial agents. This study aims to evaluate the antibacterial effects of synthesized silver nanoparticles against the pathogenic microorganisms S. aureus, P. aeruginosa, and Escherichia coli. The Silver nanoparticles were characterized using UV–vis spectroscopy, Dynamic Light Scattering (DLS), Field Emission Scanning Electron Microscopy (FESEM), and Transmission Electron Microscopy (TEM). The nanoparticles had an average size of 52 nm and exhibited an absorption peak at 430 nm. Both S. aureus and P. aeruginosa demonstrated zones of inhibition when exposed to the silver nanoparticles, indicating their potent antibacterial activity. This study highlights the potential of silver nanoparticles as effective antibacterial agents in the healthcare industry, particularly in combating hospital-acquired infections.

Cultural Perspectives on the Sustainable Use and Added Value of Plant-Based Food Dyes—A Case Study from Bulgaria

Raised personal health awareness and social environmental responsibility put pressure on the agri-food industry to adopt more sustainable ways of production, including the use of more natural ingredients, reducing waste, conservation and the regeneration of resources and energy. Plant-based colorants are ecologically friendly alternatives to artificial food dyes, especially with regards to the current reports on the adverse effects of some of the latter on human health. Various plants are traditionally used by many cultures to obtain vivid food coloration; however, the knowledge and means to produce them becomes less and less accessible to urbanized societies, and affordable organic alternatives are not always available on the market. An online questionnaire was performed to explore the awareness on plant-based dyes and pro-environmental attitudes of Bulgarian customers through the lens of Orthodox Easter eggs dyeing and the obtaining of plant dyes. From a total of 294 adult participants, only 5% reported a strict preference for natural dyes, while more than half of them (54%) were found to use natural and artificial ones concomitantly or switching between both. Of 45 plant taxa used for egg coloration, 12 were most frequently cited with many new additions of imported plants. Most of the used plant-based dyes were common fruits, spices, herbal infusions and even food waste like onion peels and avocado pits that were readily available from home gardens, markets and food shops. Additionally, we made a review of the scientific literature regarding their antioxidant and antimicrobial activity against food spoilage bacteria and foodborne pathogens isolated from eggs. All frequently used taxa were reported to exhibit antibacterial activities against Gram-positive and Gram-negative bacteria and possess antioxidant activity due to the presence of various polyphenols, essential oils and other compounds. Grape and red wine, roselle and stinging nettle are the species with the most diverse antibacterial activity, effective against 15 out of the 16 bacterial species of spoilage and foodbourn microorganisms included in our focus. The antimicrobial activities, however, were found mostly tested against bacterial strains in vitro, and further studies are needed to confirm their potential antibacterial activity when applied to Easter/boiled eggs or other food products. Our findings suggest that traditional cultural practices, as a multifaceted and engaging phenomenon, have the potential to promote environmental responsibility and a healthy lifestyle using both contemporary and traditional knowledge.