Minimum Inhibitory Concentration Values Research Articles

Green synthesis and characterization of NiO/Hydroxyapatite nanocomposites in the presence of peppermint extract and investigation of their antibacterial activities against Pseudomonas aeruginosa and Staphylococcus aureus

In many areas, antibiotic resistance is becoming a serious concern for public health. As a result of the interesting structural properties of nanomaterials, nanoscience-based methods have emerged as promising ways to increase the movement of existing antimicrobials. In this study, pristine nickel oxide (NiO) nanoparticles, hydroxyapatite (HAP) nanoparticles, and binary nickel oxide/hydroxyapatite (NiO/HAP) nanocomposites were fabricated through peppermint extract-assisted green route. The obtained results revealed that peppermint extract can be a superior green capping agent for the preparation of NiO, HAP, and NiO/HAP nanomaterials. The bioactivity tests revealed the bactericidal and anti-biofilm activities of synthesized NiO, HAP, and NiO/HAP nanostructures against Pseudomonas aeruginosa (PAO1) and Staphylococcus aureus (ATCC 43300) bacteria. The findings confirmed that the prepared NiO/HAP nanocomposites have more effective antibacterial activity than pure NiO and HAP. For Staphylococcus aureus, the minimal inhibitory concentration (MIC) values for NiO, HAP, and NiO/HAP nanocomposites were determined to be of about 9.60, 13.03, and 3.41 mg/mL, respectively. For Pseudomonas aeruginosa, the MIC values for NiO, HAP, and NiO/HAP nanocomposites were estimated as 9.6, 13.50, and 1.7 mg/mL, respectively. Although, all synthesized samples are remarkable in their ability to prevent the formation of biofilms at MIC and sub-MIC concentrations (p < 0.01), NiO/HAP illustrated biofilm inhibitory activity up to 95 % for Pseudomonas aeruginosa and to 81 % for Staphylococcus aureus. In the present study, it was demonstrated that NiO/HAP nanocomposites prepared in a green environment can be excellent antibacterial agents against Staphylococcus aureus and Pseudomonas aeruginosa.

Phytofabrication, characterization and investigation of biological properties of Punica granatum flower-derived silver nanoparticles

Due to the exceeding need to the fabrication metal nanoparticles (NPs) for different applications, exploring innovative eco-friendly approaches for the synthesis of these NPs has attracted significant attention. The objective of this study is to synthesize silver nanoparticles (AgNPs) using the aqueous extract of Punica granatum flowers. Furthermore, it aims to examine the different biological properties of these NPs, such as their antibacterial, antioxidant, anticoagulant, alpha-amylase inhibition, bacterial biofilm inhibition, and bacterial biofilm degradation activities. The AgNPs were characterized using several techniques, including UV–visible (UV–vis) spectroscopy, and Field emission scanning electron microscopy (FE-SEM). Dynamic light scattering (DLS) spectroscopy, X-ray diffraction (XRD) spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy. The AgNPs were spherical in shape, and they had a Z-average diameter of 40.50 nm and a zeta potential of −19.5 mV. The AgNPs, at a concentration of 1000 µg.mL−1, represented in vitro antioxidant and α-amylase inhibition performance of 73.19 ± 1.02 % and 73.84 ± 1.75 %, respectively. Interestingly, the AgNPs exhibited antibacterial activity at phenotypic and molecular levels against Staphylococcus aureus and Acinetobacter baumannii with minimum inhibitory concentration (MIC) value of 32 and 16 µg.mL−1, respectively. AgNPs effectively downregulated the biofilm formation of icaA and icaD genes in S. aureus, with a stronger impact on icaA, though tetracycline exhibited superior inhibition overall at the concentration of MIC. In A. baumannii, AgNPs reduced the expression of the biofilm formation pgaA and bfmsS genes, but not bfmsR, while tetracycline suppressed all three genes at the concentration of MIC. By addressing these novel aspects, this study aims to advance the field of green nanotechnology and open new avenues for the application of biogenic AgNPs in various domains.

Design, Synthesis, and Evaluation of Antifungal Activity of Pyrazoleacetamide Derivatives.

Fungal infections have posed a big challenge in the management of their treatment. Due to the resistance and toxicity of existing drug molecules in the light of pandemic infections, like COVID-19, there is an urgent need to find newer derivatives of active molecules, which can be effective in fungal infections. In the present study, we aimed to design pyrazole derivatives using molecular modeling studies against target 1EA1 and synthesize 10 molecules of pyrazole derivatives using a multi-step synthesis approach. Designed pyrazole derivatives were synthesized by conventional organic methods. The newly synthesized pyrazole molecules were characterized by using FT-IR, 1HNMR, 13CNMR, and LC-MS techniques. Molecular docking studies were also performed. The antifungal activity of newly synthesized compounds was assessed in vitro against Candida albicans and Aspergillus niger using the well plate method. Two of the compounds, OK-7 and OK-8, have been found to show significant docking interaction with target protein 1EA1. These two compounds have also been found to show significant anti-fungal activity against Candida albicans and Aspergillus nigra when compared to the standard fluconazole. The Minimum Inhibitory Concentration (MIC) value of these two compounds has been found to be 50 μg/ml. Pyrazole derivatives with -CH3, CH3O-, and -CN groups have been found to be active against tested fungi and can be further explored for their potential as promising anti-fungal agents for applications in the field of medicinal chemistry.

Synthesis of Chalcones, Screening In silico and In vitro and Evaluation of Helicobacter pylori Adhesion by Molecular Docking.

We synthetized 10 hydroxylated and methoxylated chalcones and evaluated them targeting MMP-9 inhibition, looking for the rate of adhesion of H. pylori in gastric cells, and then, reduction of the inflammatory response as alternative therapeutic agents for controlling the infection. Helicobacter pylori is a Gram-negative bacterium that chronically infects the human stomach, a risk factor for the development of inflammatory gastrointestinal diseases, including cancer, and is classified as a group I carcinogen. It is estimated that it infects around 45% of the global population and that the persistence of the infection is related to the adhesion of the bacteria in the gastric epithelium. The progression of gastric lesions to cancer is connected to the activation of the NF-κB and MAPK pathways, especially in cagA+ strains, which are related to increased expression of MMP-9. The activation of these metalloproteinases (MMPs) contributes to the adhesion of the bacterium in gastric cells and the evolving stages of cancer, such as enabling metastasis. Due to the increasing resistance to the current therapy protocols, the search for alternative targets and candidate molecules is necessary. In this way, controlling adhesion seems to be a suitable option since it is a crucial step in the installation of the bacterium in the gastric environment. Synthetize ten hydroxylated and methoxylated chalcones. Assess their anti-H. pylori potential, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). Evaluate their cytotoxicity in AGS cells and selectivity with L-929 cells. Analyze the results and correlate them with in silico predictions to evaluate potential anti-adhesive properties for the chalcones against H. pylori. The chalcones were synthetized by Claisen-Schmidt condensation using Ba(OH)2 or LiOH as catalysts. Predictive in silico assays in PASS Online, tanimoto similarity, ADME properties and molecular docking in MMP-9 (PDB code: 6ESM) were performed. The in vitro assays carried out were the cell viability in gastric adenocarcinoma cells (AGS) and fibroblasts (L-929) by the MMT method and anti-H. pylori, by the broth microdilution method, through the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Ten chalcones were synthesized through Claisen-Schimdt condensation with yields of 10 to 52% and characterized by 1H and 13C nuclear magnetic resonance (NMR) and mass spectrometry (MS). in silico data revealed the possibility of anti-H. pylori, anti-inflammatory, and MMP-9 inhibition for the chalcones. Chalcone 9 showed the best growth inhibition values for MIC and MBC, at 1 μg/mL and 2 μg/mL, respectively. Chalcones 14 and 15 likewise demonstrated excellent inhibitory results, being 2 μg/mL for both MIC and MBC. Additionally, 15 had the best MMP-9 inhibition score. Despite not corroborating the in silico findings, chalcones 10, 13, and 18 showed good cytotoxicity and the best selectivity indices. All compounds exhibited strong activity against H. pylori, specially 15. The predicted MMP-9 inhibition by molecular docking added to the reasonable SI and CI50 values for 15 and the satisfactory reduction in the rate of survival of the bacteria, reveals that it may be acting synergically to reduce the inflammatory response and the possibilities for developing a tumor by inhibiting both bacteria and malignant cells.

Evaluation of Novel HLM Peptide Activity and Toxicity against Planktonic and Biofilm Bacteria: Comparison to Standard Antibiotics.

Antibiotic resistance is one of the main concerns of public health, and the whole world is trying to overcome such a challenge by finding novel therapeutic modalities and approaches. This study has applied the sequence hybridization approach to the original sequence of two cathelicidin natural parent peptides (BMAP-28 and LL-37) to design a novel HLM peptide with broad antimicrobial activity. The physicochemical characteristics of the newly designed peptide were determined. As well, the new peptide's antimicrobial activity (Minimum Inhibitory Concentration (MIC), Minimum Bacterial Eradication Concentration (MBEC), and antibiofilm activity) was tested on two control (Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922) and two resistant (Methicillin-resistant Staphylococcus aureus (MRSA) ATCC BAA41, New Delhi metallo-beta- lactamase-1 Escherichia coli ATCC BAA-2452) bacterial strains. Furthermore, synergistic studies have been applied to HLM-hybridized peptides with five conventional antibiotics by checkerboard assays. Also, the toxicity of HLM-hybridized peptide was studied on Vero cell lines to obtain the IC50 value. Besides the percentage of hemolysis action, the peptide was tested in freshly heparinized blood. The MIC values for the HLM peptide were obtained as 20, 10, 20, and 20 μM, respectively. Also, the results showed no hemolysis action, with low to slightly moderate toxicity action against mammalian cells, with an IC50 value of 10.06. The Biomatik corporate labs, where HLM was manufactured, determined the stability results of the product by Mass Spectrophotometry (MS) and High-performance Liquid Chromatography (HPLC) methods. The HLM-hybridized peptide exhibited a range of synergistic to additive antimicrobial activities upon combination with five commercially available different antibiotics. It has demonstrated the biofilm-killing effects in the same concentration required to eradicate the control strains. The results indicated that HLM-hybridized peptide displayed a broad-spectrum activity toward different bacterial strains in planktonic and biofilm forms. It showed synergistic or additive antimicrobial activity upon combining with commercially available different antibiotics.

Effects of Petasitin as Natural Extract on Proliferation and Pathological Changes of Pediatric Neuroblastoma SK-N-SH Cells

Scalp alopecia areata (SAA) is a common non-scarring hair loss condition, associated with factors such as autoimmune responses, genetics, emotional stress, and endocrine imbalances. Current treatments for SAA included minoxidil, topical steroid creams, biologics, and plant extracts. Tea tree oil (TTO), a natural plant extract, is known for its antibacterial, anti-inflammatory, and acaricidal properties, and it also provides nourishment for hair. In this research, a natural extract of TTO, was prepared to analyze its antibacterial properties. The hair follicle stem cells (HFSCs) of patients with primary SAA were analyzed to understand the influences of TTO on migration of HFSCs. TTO was extracted from fresh tea tree leaves using steam distillation. Quantitative analysis of gas chromatography-mass spectrometry (GC/MS) qualitative analysis and its total ion chromatogram using area normalization method were conducted. Meanwhile, its antibacterial activity was tested against five common pathogens (Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Staphylococcus albus (S. albus), Pseudomonas aeruginosa (P. aeruginosa), and Candida albicans (C. albicans)) by measuring the diameter of inhibition zones (DIZ), minimal inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). HFSCs were isolated from patients with SAA and cultured in vitro, with cell identification performed through cytokeratin 15 (K15) immunofluorescent staining. The HFSCs were then exposed to varying concentrations (0.0, 0.5, 2.0, 5.0, 10.0, and 25.0 mmol/L) of TTO for culture, and cell proliferation activity (CPA) was assessed using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay, while migration of HFSCs was evaluated using the Transwell chamber assay. Results demonstrated that the extracted TTO had a content of 0.69 g and an extraction rate of 2.32%. 36 components were identified, constituting 98.67% of the total, with 4-terpineol reaching a high concentration of 48.35%. It exhibited a DIZ of less than 25 mm against all tested pathogens, with MIC values lower than 29 mg/mL and MBC values below 38 mg/mL. Patients with SAA displayed yellow and black dots, broken hair, malnourished and exclamation mark hairs, with few flag hairs observed in skin microscope examination. Isolated and cultured HFSCs expressed K15 primarily in the cytoplasm and exhibited favorable growth dynamics. Treatment with various concentrations of TTO greatly increased CPA and migrated cell numbers in HFSCs, with the optimal effect observed at 5.0 mmol/L concentration of TTO. In conclusion, the plant extract TTO possessed significant antibacterial activity and can promote proliferation and migration in vitro of HFSCs, suggesting its potential therapeutic application for SAA.

Antibacterial effects of Psidium guajava leaf extracts on diarrhea caused by Salmonella typhimurium and Escherichia coli in sheep

Diarrhea in neonatal ruminants, especially sheep, poses a serious challenge in livestock management, often leading to high mortality rates. The primary pathogens responsible are Salmonella typhimurium and Escherichia coli. This study explores the antibacterial potential of Psidium guajava (guava) leaf extracts as an alternative to conventional treatments. Guava leaves, collected from Tubah subdivision, Mezam, were processed into aqueous and ethanolic extracts. Phytochemical analysis revealed the presence of bioactive compounds including resins, alkaloids, saponins, glycosides, tannins, and flavonoids. Antibacterial activity was assessed using agar well diffusion and Minimum Inhibitory Concentration (MIC) methods. The aqueous extract displayed dose-dependent antibacterial effects, with inhibition zones of 16.0 mm against E. coli and 15.2 mm against S. typhimurium at 100 mg/ml, which were less effective compared to Gentamycin (19 mm). The MIC values for the aqueous extract were 6.25–3.13 mg/ml for E. coli and 12.5–6.25 mg/ml for S. Typhimurium. In contrast, the ethanolic extract showed slightly superior efficacy with inhibition zones of 16.2 mm for E. coli and 17.6 mm for S. Typhimurium at 100 mg/ml. The MIC values for the ethanolic extract were 3.13–1.56 mg/ml for E. coli and 6.25–3.13 mg/ml for S. typhimurium, indicating higher potency than the aqueous extract. Conclusively, both guava leaf extracts exhibit significant antibacterial properties, with the ethanolic extract being more potent. These results validate the traditional use of Psidium guajava and suggest its potential as a natural antimicrobial agent, though further research is needed to optimize its therapeutic applications.

Effect of mutation of secG gene in drug resistance and physiological and biochemical activities of Xanthomonas oryzae pv. oryzae.

Bacterial leaf blight caused by the bacterium Xanthomonas oryzae pv. oryzae has a substantial effect on the yield of rice crops. The secretory (Sec) pathway, essential for efflux transport in bacteria, remains insufficiently studied in X. oryzae pv. oryzae, especially regarding its roles in drug resistance and physiology. This study involved transcriptome analysis on two X. oryzae pv. oryzae strains: a secG deletion strain (∆secG) and its complemented strain (C: ∆secG). In comparison to the parental strain PXO99A, ∆secG exhibited slower growth, with reductions in swimming (20.67%) and swarming (12.59%), while maintaining 76.7% of its biofilm formation capacity and 63.6% of exopolysaccharide production. The minimum inhibitory concentration (MIC50) values for an n-butanol extract of Bacillus velezensis HN-2 (HN-2E) and bacitracin against ∆secG were 0.426 μg/mL (5.3% lower than that of PXO99A) and 10.905 μg/mL, respectively. Notably, ∆secG exhibited increased susceptibility to hydrogen peroxide (H2O2), being inhibited at 0.25 mm compared to 0.3 mm for PXO99A and C: ∆secG. In the presence of 0.2 mM H2O2, the susceptibility of ∆secG to HN-2E increased by 31.22% (MIC50 = 0.159 μg/mL), while PXO99A and C: ∆secG exhibited MIC50 values of 0.280 and 0.291 μg/mL, respectively. Our findings demonstrate that Bacillus-induced H2O2 production enhances the sensitivity of X. oryzae pv. oryzae to biocontrol agents, providing valuable insights for the prevention of bacterial leaf blight. These results highlight the significance of the Sec pathway in the behavior and resistance of X. oryzae pv. oryzae, as well as potential areas for further research on plant diseases. © 2024 Society of Chemical Industry.

Deciphering physical and functional properties of chitosan-based particles for agriculture applications

Traditional methods for controlling plant pathogens rely on toxic chemicals, posing environmental and health risks. Developing sustainable, eco-friendly alternatives is crucial. Chitosan (CS)-based materials offer promising solutions for sustainable agriculture. We aimed to synthesize and characterize CS-based microparticles with varying properties and assess their antimicrobial performance to establish correlations between variations in physicochemical characteristics and their impact on performance within biological systems. We adjusted the synthesis parameters, producing particles labeled P1, P2, and P3, which have sizes of 0.19 ± 0.07 μm, 0.45 ± 0.32 μm, and 1.22 ± 0.32 μm, and zeta potentials of +7.6 ± 4.25 mV, +22 ± 3.51 mV, and + 12.9 ± 4.54 mV, respectively. Extensive toxicological screenings showed that these CS-based microparticles were non-toxic across cell cultures, mouse red blood cells, soil microbiota, nitrogen-cycling bacteria, and plant toxicity assays. Encouraged by these results, we evaluated their antimicrobial potential against economically important crop pathogens. The CS-based microparticles exhibited antimicrobial effects against the bacterium Pseudomonas syringae pv. tomato DC3000 and the fungus Fusarium solani f. sp. eumartii. Higher zeta potentials correlated with greater antimicrobial efficacy, evidenced by lower IC50 and minimum inhibitory concentration (MIC) values. These findings indicate that all three microparticles analyzed displayed antimicrobial activity against two economically significant crop pathogens, with P2 showing solid performance attributed to its physicochemical characteristics. Therefore, CS-based microparticles represent a promising, nontoxic, and environmentally friendly alternative for modern agriculture, with their biological activities potentially predictable through careful selection of physicochemical properties before the synthesis process.

Population pharmacokinetics and dose optimization of ceftazidime in critically ill children

ObjectiveThe aim of this study was to develop a population pharmacokinetic model for ceftazidime in critically ill children in the pediatric intensive care unit (PICU) and optimize an appropriate dosing regimen for this population.MethodsWe performed a prospective pharmacokinetic study on critically ill children aged 0.03–15 years. A population pharmacokinetic model was developed using the NLME program. Statistical and graphical methods were used to assess the stability and predictive performance of the model. Monte Carlo simulations were conducted to determine the optimal ceftazidime dosing regimen to achieve 70% fT &amp;gt; minimum inhibitory concentration (MIC).ResultsThis study included 88 critically ill children and 100 ceftazidime serum concentrations. The pharmacokinetic characteristics of ceftazidime were best described by a one-compartment linear elimination model. The weight and estimated glomerular filtration rate (eGFR) were determinant covariates for the clearance (CL) of ceftazidime. The recommended ceftazidime dosage regimens achieved a probability of target attainment (PTA) &amp;gt;90% for critically ill children at MIC values of 2, 4, and 8 mg/L. For bacterial infection at an MIC of 16 mg/L, it is difficult to achieve effective pharmacodynamic (PD) targets in vivo with the commonly used dose of ceftazidime.ConclusionThe population pharmacokinetic model of ceftazidime was established in critically ill children. Based on this model, we recommend evidence-based, individualized dosing regimens for subgroups with different weights and renal functions. The current daily dosage for children adequately meets the treatment requirements for MICs of 2, 4, and 8 mg/L, while for bacterial infection at an MIC of 16 mg/L, an elevated dosage regimen may be required.Clinical Trial Registrationhttps://www.medicalresearch.org.cn/login, Identifier MR-42-22-000220.

Mesoporous silica nanoparticles co-loaded with lysozyme and vancomycin for synergistic antimicrobial action

Nanotechnology offers a novel strategy for enhancing the susceptibility of pathogens resistant to traditional antibiotics. Another effective strategy is combination therapy, where multiple agents are used together to improve treatment efficacy. In this study, both nanoparticle-based formulation and combinatorial therapy were utilized to develop a potent antibacterial system targeting infectious bacteria. Lysozyme (Lys) and Vancomycin (Van) were co-loaded onto mesoporous silica nanoparticles (MSNs), forming Lys-Van-MSNs. The antimicrobial activity of these nanoparticles was evaluated by determining the minimum inhibitory concentration (MIC) against Staphylococcus aureus. The MIC values for Lys-Van-MSNs were 0.85 µg/ml for Van and 0.168 mg/ml for Lys, reflecting reductions of 86.4% and 93.7%, respectively, compared to the free forms. Additionally, cytotoxicity was tested using MTT, ROS, and hemolysis assays on human cell lines (breast, fibroblast, and AGS), showing over 80% cell viability, indicating minimal toxicity. The MSN-based formulation, with its synergistic antibacterial effects, reduced drug dosage, and high biocompatibility, offers a practical and effective solution for addressing bacterial infections.

In-Vitro Activity of Dimercaptosuccinic Acid in Combination with Carbapenems Against Carbapenem-Resistant Pseudomonas aeruginosa.

Carbapenenemase producers, particularly the metallo-β-lactamase (MBL) types in Pseudomonas aeruginosa, have emerged as an urgent threat in health care settings. MBLs require zinc at their catalytic site and can be inhibited by dimercaptosuccinic acid (DMSA), a metal chelator known for the treatment of lead and mercury intoxication. Isogenic strains of wild-type and OprD-deleted P. aeruginosa PA14, were constructed, producing the MBLs VIM-2, NDM-1, SPM-1, IMP-1, and AIM-1, or the non-MBL carbapenemases, GES-5 and KPC-2. In addition, 59 previously characterized clinical isolates of P. aeruginosa producing different ß-lactamases (including carbapenemases), and with known outer-membrane porin OprD status, were utilized. Minimal inhibitory concentrations values of imipenem and meropenem, and DMSA combinations were determined, and time-kill assays were performed with PA14 expressing VIM-2. Results indicated a significant additive effect of DMSA (most effective at 3 mM) and carbapenems in recombinant and clinical strains of P. aeruginosa expressing MBLs, in particular against VIM producers, which are the most prevalent carbapenemases in P. aeruginosa. This effect was best evidenced with meropenem and in strains without OprD modification. DMSA shows promising efficacy, particularly in combination therapy with meropenem, for treating infections caused by MBL-producing P. aeruginosa.

Transition Metal Complexes of Turmeric Schiff Base: A New Avenue for the Development of Antioxidant, Anti‐Inflammatory, and Preliminary Anticancer Therapies via In Silico, In Vitro, and In Vivo Assessments

ABSTRACTIn the current study, Knoevenagel condensates mediated by ultrasound were created using cinnamaldehyde and physiologically active curcumin. These Knoevenagel condensates have been reacted with 4‐aminoantipyrene to create curcumin Schiff bases. The octahedral geometry of the synthesized transition metal complexes is verified by a range of analytical methods and spectroscopic techniques. It is interesting to note that viscosity tests against calf thymus‐DNA and UV–visible absorption titration are used to confirm the synthetic drugs intercalative binding effectiveness. VLS3D online program was utilized to examine the properties of SWISS ADME. The experimental validation of antioxidant and anti‐inflammatory activity demonstrates that theoretical expectations align with the experimental findings. The minimum inhibitory concentration values of the synthesized complexes show that they are more effective against microbes than ligand. Density functional theory simulations were performed at the B3LYP/6–31G(d) level to examine the complexes' thermodynamic stability and physiological accessibility. Every synthetic molecule has been docked against the bovine serum albumin 3v03 enzyme.

Variability in cadmium tolerance of closely related Listeria monocytogenes isolates originating from dairy processing environments.

Mobile genetic elements in Listeria monocytogenes contribute to its survival in natural and food processing environments. This study focused on how different genetic variants of the efflux pump gene cadAC and group of closely related cadA1C1 strains respond to cadmium exposure. When exposed to two cadmium salts, cadmium chloride and cadmium sulfate, we observed varying growth patterns, with a significantly longer lag phase in cadmium sulfate compared to cadmium chloride. Strains with cadA1 to cadA3 had similar growth trends, whereas a strain with the cadA4 variant had the highest minimum inhibitory concentration value. Among 88 strains from dairy processing facilities, significant phenotypic differences were observed despite core genome similarities, indicating other underlying genetic and physiological factors contribute to cadmium tolerance. Since cadmium tolerance studies in L. monocytogenes are limited, with rare phenotypic comparisons between closely related strains, our study makes an important observation and contribution to understanding of L. monocytogenes tolerance to cadmium by providing phenotypic comparisons between numerous strains within the same clonal group (<16 single nucleotide polymorphisms).

Genotyping and drug susceptibility profiling of Prototheca sp. strains isolated from cases of protothecosis in dogs.

Protothecosis in dogs is a rare, yet emerging disease, distinguished by its often-aggressive clinical course and high fatality rate. Our study was conducted to enhance treatment protocols for affected dogs by better understanding the genetic diversity and drug resistance patterns of Prototheca species. To identify species and drug susceptibility profiles of an international collection of 28 Prototheca strains isolated from cases of protothecosis in dogs. None. Retrospective study. Species-level identification was made for isolates from 28 dogs in 6 countries by molecular typing with the partial cytb gene as a marker. For the determination of minimum inhibitory concentrations (MICs) and minimum algicidal concentrations (MACs), the Clinical Laboratory Standards Institute (CLSI) protocol (M27-A3) was used. Prototheca bovis was the most prevalent species, accounting for 75% (21/28) of the cases, followed by P. wickerhamii (18%; 5/28) and P. ciferrii (7%; 2/28). Of the 6 drugs tested, efinaconazole (EFZ) was the most potent in vitro, with its median MIC and MAC values equal to 0.125 mg/L. The lowest activity was found for fluconazole (FLU), with MIC and MAC medians of 48 mg/L and 64 mg/L, respectively. Our study identifies P. bovis as the species that most frequently causes protothecosis in dogs, which suggests the possibility of cross-species infection from other animals, especially cows. Additionally, it indicates that EFZ could be used in the treatment of infection in the colon.

Antibacterial Activity of Ethanolic Extract of Cardiospermum halicacabum against Methicillin-Resistant Staphylococcus aureus

We investigated the antibacterial activity of Cardiospermum halicacabum extract against methicillin-resistant Staphylococcus aureus (MRSA) via the disk diffusion method and identified the plant’s bioactive phytochemicals. Additionally, we evaluated the synergistic effects, and primary mechanism of action of the plant extract against the S. aureus strain PB57 (MRSA). The ethanolic extract of C. halicacabum contained beneficial secondary metabolites such as the flavonoids apigenin, terpenoids and tannins. The total phenolic content, expressed as the gallic acid equivalent (g GAE/kg), was 87.66 ± 14.56 g GAE/kg at a concentration of the 1 mg/mL. The plant extract inhibited and killed the S. aureus strain PB57 with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.98 mg/mL. Electron microscopy revealed that the plant extract caused damage to the ultrastructures of the cells of the pathogens. The compounds in the extract remained below known maximum acceptable cytotoxicity thresholds for fibroblast cells, which are typically in the range of [include specific value from relevant guidelines or literature]. Further cytotoxicity assays are required to determine the precise safety margins for therapeutic use. Although the extract showed promise against MRSA, its application as a broad treatment for infectious diseases requires more specific testing on other pathogens. Based on the scope of our research, C. halicacabum could be a viable candidate for the development of treatments targeting MRSA-related infections. HIGHLIGHTS Our investigation revealed that the ethanolic extract of Cardiospermum halicacabum exhibited significant antibacterial activity against the methicillin-resistant Staphylococcus aureus (MRSA) strain PB57. The extract contained beneficial secondary metabolites, including flavonoids such as apigenin, as well as terpenoids and tannins. Moreover, the electron microscope shown that the extract disrupted the pathogen’s cell structures and, despite showing some cytotoxicity at higher doses, remained within safe limits, positioning C. halicacabum as a potential treatment for infectious diseases. GRAPHICAL ABSTRACT

Antitubercular Activity of 7-Methyljuglone-Loaded Poly-(Lactide Co-Glycolide) Nanoparticles.

Loading of natural products into poly-(lactide-co-glycolic) acid (PLGA) nanoparticles as drug delivery systems for the treatment of diseases, such as tuberculosis (TB), has been widely explored. The current study investigated the use of PLGA nanoparticles with 7-methyljuglone (7-MJ), an active pure compound, isolated from the roots of Euclea natalensis A. DC. 7-MJ as well as its respective PLGA nanoparticles were tested for their antimycobacterial activity against Mycobacterium smegmatis (M. smegmatis), drug-susceptible Mycobacterium tuberculosis (M. tuberculosis) (H37Rv), and multi-drug-resistant M. tuberculosis (MDR11). The cytotoxicity of 7-MJ as well as its respective PLGA nanoparticles were tested for their cytotoxic effect against differentiated human histiocytic lymphoma (U937) cells. Engulfment studies were also conducted to determine whether the PLGA nanoparticles are taken up by differentiated U937 cells. 7-MJ has been shown to have a minimum inhibitory concentration (MIC) value of 1.6 µg/mL against M. smegmatis and multi-drug-resistant M. tuberculosis and 0.4 µg/mL against drug-susceptible M. tuberculosis. Whilst promising, 7-MJ was associated with cytotoxicity, with a fifty percent inhibition concentration (IC50) of 3.25 µg/mL on differentiated U937 cells. In order to lower the cytotoxic potential, 7-MJ was loaded into PLGA nanoparticles. The 7-MJ PLGA nanoparticles showed an 80-fold decrease in cytotoxic activity compared to free 7-MJ, and the loaded nanoparticles were successfully taken up by differentiated macrophage-like U937 cells. The results of this study suggested the possibility of improved delivery during TB therapy via the use of PLGA nanoparticles.

Photodynamic Inactivation of Bacteria Using Nickel(II) Complexes with Catecholate and Phenanthroline Ligands.

Metal complexes activated by light can combat infections by triggering the photodynamic inactivation of bacteria. Herein, we report six mixed-ligand nickel(II) complexes with the formulation [Ni(NN)2(L)] (1-6), where NN represents an N,N-donor phenanthroline ligand, specifically 1,10-phenanthroline (phen in 1, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 3, 4), and dipyrido[3,2-a:2',3'-c]phenazine (dppz in 5, 6), while L is an O,O donor bidentate ligand derived from catechol (cat2-, in 1, 3, 5) or esculetin (esc2-, in 2, 4, 6). The paramagnetic d8 octahedral complexes demonstrated good dark and photostability in the solution phase and exhibited significant light absorption in the visible (400-700 nm) region. When exposed to low-energy visible light, these complexes demonstrated significant photodynamic inactivation activity against both gram-(+) S. aureus and gram-(-) E. coli bacteria. This resulted in minimum inhibitory concentration (MIC) values ranging from 0.2 to 5.0 μg/mL. The activity was caused by the cell-damaging singlet oxygen species produced by the complexes under light exposure. Notably, the complexes showed no bacterial inhibition activity under dark conditions. This study marks the first examples of Ni(II) complexes designed for light-triggered antibacterial activity, illuminating the path for Ni(II)-based non-macrocyclic complexes for antibacterial PDT applications.

Enhancing Antimicrobial Activity of Thyme Essential Oil Through Cellulose Nano Crystals-Stabilized Pickering Emulsions.

Essential oils (EOs), such as thyme essential oil (TEO), are widely known for their antimicrobial properties; however, their direct application in food systems is limited due to their poor stability, which affects their efficacy. This study aims to improve the stability and antimicrobial efficacy of TEO by encapsulating it in Pickering emulsions stabilized with cellulose nanocrystals (CNC). Two formulations of Pickering emulsions with 5% and 10% TEO were prepared and compared to traditional surfactant-based emulsions. The stability of the emulsions was assessed over 21 days, and particle size, zeta potential, Raman spectroscopy, and FTIR were used for characterization. The antimicrobial activity was tested against several foodborne pathogens, with minimum inhibitory concentration (MIC) values determined. The 10% TEO Pickering emulsion showed antimicrobial activity, with MIC50 values of 4096 µg/mL against Staphylococcus aureus and Escherichia coli, while the 5% TEO formulation had no effect at MIC50 > 8192 µg/mL. The CNC-stabilized Pickering emulsions exhibited superior stability, showing no phase separation over 21 days. The findings suggest that CNC-stabilized Pickering emulsions are effective at improving the stability and antimicrobial performance of TEO, making them a promising natural preservative for food packaging and safety. Further research is recommended to optimize the formulation and broaden TEO's application in food preservation.

Physicochemical properties, GC–MS profiling, and antibacterial potential of Allium sativum essential oil: In vitro and in silico approaches

Antibiotic resistance remains a critical challenge for public health. In this study, we investigate the antibacterial potential of Moroccan Allium sativum L. essential oil (EO) through both in vitro and in silico approaches. The EO was extracted using hydrodistillation, and its physicochemical properties were analyzed alongside its chemical composition via gas chromatography-mass spectrometry (GC/MS). We assessed antibacterial efficacy through disk diffusion assays targeting Escherichia coli (E. coli), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa (P. aeruginosa), and determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Finally, an in silico molecular docking analysis and ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction were performed. Our analysis identified 13 sulfur-based compounds within the EO, with diallyl disulfide (42.85 %), methylallyl disulfide (18.84 %), methylallyl trisulfide (15.38 %), and diallyl trisulfide (13.11 %) as major constituents. The EO demonstrated robust activity against MRSA, with an inhibition zone of 22 mm and an MIC of 0.75 mg/mL, whereas E. coli exhibited lower sensitivity, with an MIC of 1.51 mg/mL. Molecular docking analysis suggested that the primary sulfur compounds may effectively inhibit bacterial resistance-related enzymes. These findings highlight the potential of Allium sativum L. EO as a natural antibacterial agent, attributed largely to its sulfur compound content. This activity is likely linked with the EO's interaction with the complex structures of bacterial cell membranes, offering promise in combating resistant bacterial strains.