Gram-positive Bacterial Strains Research Articles

A Topical Alginate-Based Wound Gel Fixated with Metal-Based Nanoparticles and Tranexamic Acid as a Hemostatic Wound Healing System

AbstractWounds are usually accompanied by complications such as excessive bleeding and bacteria invasion. The design of wound dressings that rapidly stop excessive bleeding and inhibit bacterial invasion, is crucial to promoting accelerated wound healing. To meet the abovementioned requirements in wound dressings, topical gels were prepared from sodium alginate (SA) and carbopol. The wound dressings were loaded with an antifibrinolytic agent, tranexamic acid, and a variety of metal-based nanoparticles. The prepared topical gels displayed significant antibacterial efficacy against Gram-negative bacteria and moderate activity against Gram-positive bacterial strains. These gels exhibited good spreadability and viscosity, signifying suitability for skin application, and ease of application. Moreover, the prepared gels showed good cytocompatibility, promoted cell proliferation, and exhibited > 85% wound closure on day 3 compared to the untreated which showed a 38% wound reduction in vitro. Excellent blood clotting absorbance values were observed for the gels compared to the control, showing that they can promote blood clotting. Features presented by the prepared gels reveal that they are promising wound dressings for treating bleeding and infected wounds.

Antibactericidal Ir(III) and Ru(II) Complexes with Phosphine-Alkaloid Conjugate and Their Interactions with Biomolecules: A Case of N-Methylphenethylamine.

The phosphine ligand (Ph2 PCH2 N(CH3 )(CH2 )2 Ph, PNMPEA) obtained by the reaction of the (hydroxymethyl)diphenylphosphine with naturally occurring alkaloid N-methylphenethylamine, was used to synthesize the half-sandwich iridium(III) (Ir(η5 -Cp*)Cl2 Ph2 PCH2 N(CH3 )(CH2 )2 Ph, IrPNMPEA) and ruthenium(II) (Ru(η6 -p-cymene)Cl2 Ph2 PCH2 N(CH3 )(CH2 )2 Ph, RuPNMPEA) complexes. They were characterized using a vast array of methods, including 1D and 2D NMR, ESI(+)MS spectrometry, elemental analysis, cyclic voltammetry (CV), electron spectroscopy in the UV-Vis range (absorption, fluorescence) and density functional theory (DFT). The initial antimicrobial activity in vitro toward Gram-positive and Gram-negative bacterial strains was examined, indicating that both complexes are selective towards Gram-positive bacteria, e. g., Staphylococcus aureus, where the IrPNMPEA has been more bactericidal compared to RuPNMPEA. Additionally, the interactions of these compounds with various biomolecules, such as DNA (ctDNA, plasmid DNA, 9-ethylguanine (9-EtG), and 9-methyladenine (9-MeA)), nicotinamide adenine dinucleotide (NADH), glutathione (GSH), and ascorbic acid (Asc) were described. The results showed that both Ir(III) and Ru(II) complexes accelerate the oxidation process of NADH, GSH and Asc that appeared to occur by an electron transfer mechanism. Interestingly, only IrPNMPEA leads to the formation of various biomolecule adducts, which can explain its higher activity. Furthermore, RuPNMPEA and IrPNMPEA have been interacting with the DNA through weak noncovalent interactions.

P-TSA-Promoted Efficient Synthesis of Some New Thiophene Hybridized Thiadiazolyl Schiff Bases as Antibacterial Agents

A new series of thiophene hybridized thiadiazolyl Schiff bases was designed and synthesized employing FeCl3-mediated cyclization of thiosemicarbazoneinto thiadiazoles and their subsequent Schiff bases formation using p-TSA in benzene. To understand the interaction of the proposed compounds with β-lactamase (Protein Data Bank [PDB] ID: 3UDI), a molecular docking was performed. All the compounds demonstrated an optimal binding affinity with β-lactamase (−8.17 to −9.75 kcal/mol) and showed crucial hydrogen bonds and π–π interaction with the leading amino acids Arg298, Ala300, and Val391 located at the active site of β-lactamase. The in vitro antibacterial activity of the desired molecules was conducted against few gram-positive and Gram-negative bacterial strains using amoxicillinas reference drug. The compound having p-hydroxyphenyl substituent (3c) was found to be potentially effective to inhibit P. aeruginosa and E. coli with MIC value 7.5 μg/mL and 9.0 μg/mL, respectively, whereas other compounds exhibited moderate to good activity. Altogether, the primary in-vitro screening of newly synthesized thiophene hybridized thiadiazole Schiff bases opens a new venture towards the development of promising alternatives of β-lactamase inhibitors as anti-bacterial agents.

Design, Synthesis, and Molecular Docking Studies of 1,3,4-Oxadiazole Scaffolds as Potential Antimicrobial Agents

In search of suitable antimicrobial compounds, we report here the synthesis, characterization, and biological activities of 2-((5-(2-nitrophenyl)-1,3,4-oxadiazol-2-yl)thio)-N-arylacetamide (5a-5p). The molecules were characterized by infrared, mass, hydrogen-1 nuclear magnetic resonance (1H NMR), 13C NMR, and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic Gram-positive and Gram-negative bacterial and fungal strains. The results were explained with a molecular docking study against microbial DNA gyrase. It was found that the compounds 5h, 5i, 5j, 5k, 5l, 5n, and 5p showed significant activities against tested organisms as compared to standard drugs (fluconazole and ciprofloxacin).

Antimicrobial activities and theoretical studies on the weak interactions formation in two different configuration complexes

The ligand 2-(3-pyrazolyl)-4-methyl-1,2-dihydroquinazoline-N3-oxide (L) was synthesized, and two transition metal complexes, namely [Cu(L)2]·(NO3)2 (1) and [Ni(L)3]·(NO3)2·3CH3OH (2) were prepared through complexation reaction between L and the corresponding metal salt. L and both complexes were characterized by elemental analysis, as well as compared with spectrographic technique for example FT-IR and UV–Vis spectroscopy. X-ray single-crystal diffraction demonstrated that 1 was tetra-coordinated square planar whereas 2 was hexa-coordinated slightly distorted octahedral geometry. Meanwhile, the metal-ligand ratios were 2:1 in 1 whereas 3:1 in 2. Through the superposition of hydrogen bonds and other weak interactions, both complexes formed 1-D chain-like, 2-D layered, and 3-D supramolecular structures. Theoretical investigations explained the optimized geometries of complexes and the electrostatic potential distribution in molecules, and also analyzed the electron transition types of L and both complexes in combination with UV–vis spectroscopy, which provided theoretical support for the experimental conclusions. Electrostatic potential (ESP) was computed for both complexes to predict the reaction positions of electrophilic and nucleophilic assaults. Hirshfeld Surface Analysis quantified interactions in molecules and analyzed the contribution of various weak interactions to stabilize the structure of complexes. Especially, antibacterial experiments displayed compounds had certain antibacterial activities against both Gram-positive and Gram-negative bacterial strains.

A Label-Free and Ultrasensitive Prussian Blue-Based Dipstick Sensor for Bacterial and Biofilm Detection.

Water and food contamination has become the major contributor to infections and deaths. However, rapid and sensitive bacterial detection still remains an unmet demand that has attracted widespread attention. Often water and food samples are sent out for laboratory testing to detect the presence of contamination, which is time-consuming and laborious. Herein, we have developed a highly sensitive, tenable, affordable, and robust (STAR) paper-based colorimetric dipstick sensor based on the principle of Prussian blue (PB) synthesis as an indicator of bacterial contamination. In the presence of bacteria, it leads to the formation of PB, a dye that acts as a colorimetric indicator. The intensity of the PB is the direct measure of the degree of contamination. The fabrication of the STAR dipstick sensor involves a simple and cost-effective process. The STAR dipstick sensor is ultrasensitive and can detect up to 101 CFU/mL of bacteria within minutes of contact with the test sample. The STAR dipstick sensor is fabricated using biodegradable components, which is speculated to facilitate quick and environmentally friendly degradation after each use. The sensor has been validated for its properties and capabilities at different pH to detect both Gram-positive and Gram-negative bacterial strains in real-time samples. The stability and degradation were also monitored. Comprehensively, the proposed STAR dipstick sensor can serve as a point-of-care device to detect bacterial contamination in a swift and sensitive manner.

Biodegradable Polymer Composites of Metal Organic Framework-5 (MOF-5) for the Efficient and Sustained Delivery of Cephalexin and Metronidazole

The sustained and controlled delivery of antimicrobial drugs has been largely studied using nanomaterials, like metal organic frameworks (MOFs), and various polymers. However, not much attention has been given to combining MOFs and biodegradable polymers towards the potentially more sustained release of active pharmaceutical ingredients. Herein, we report a comparative study of two widely used antimicrobial drugs, cephalexin and metronidazole, from zinc-based MOF-5 incorporated into biodegradable polycaprolactone (PCL) and poly-lactic glycolic acid (PLGA) composites. Cephalexin and metronidazole were separately loaded into MOF-5 post-synthetically, followed by their integration into biodegradable PLGA and PCL composites. The pristine MOF-5 and the loaded MOFs were thoroughly characterised using Fourier-transformed infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Ultraviolet-visible (UV-Vis) spectroscopy studies were carried out to assess the release of the drugs in PBS for up to 72 h, showing a cumulative release of 24.95 wt% and 27.84 wt% for cephalexin and metronidazole, respectively. The antibacterial properties of the pristine MOF, pure drugs, drug-loaded MOFs and the loaded composites were assessed against Gram-positive and Gram-negative bacterial strains, Staphylococcus aureus or Staphylococcus epidermidis and Escherichia coli or Acinetobacter baumanii, respectively. A cephalexin-loaded MOF-5 composite of PCL (PCL-ceph@MOF-5) showed the best efficiency for the controlled release of drugs to inhibit the growth of the bacteria compared to the other composites. This study demonstrates that the combination of MOFs with biodegradable polymers can provide an efficient platform for the sustained release of antimicrobial drugs and can be a promising tool to manage antimicrobial resistance (AMR).

Assessing Spectral Analysis of Phytoconstituents and Their In Silico Interactions with Target Proteins in Plant Seed Extracts.

The pharmacological and preventive attributes of extracts from vegetable seeds have garnered widespread recognition within the scientific community. This study systematically assessed the in vitro antibacterial, antioxidant, and anti-breast cancer properties of phytochemicals present in various solvent-based vegetable seed extracts. We also conducted molecular docking simulations to ascertain their interactions with specific target proteins. Besides, nine distinct chemical constituents were identified using gas chromatography-mass spectrometry (GCMS). Remarkably, the ethyl acetate extract exhibited robust inhibitory effects against Gram-positive and Gram-negative bacterial strains. Furthermore, its capacity for 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging was found to be noteworthy, with an IC50 value of 550.82 ± 1.7 µg/mL, representing a scavenging efficiency of 64.1 ± 2.8%. Additionally, the ethyl acetate extract demonstrated significant hydrogen peroxide (H2O2) scavenging activity, with a maximal scavenging rate of 44.1 ± 1.70% (IC50) at a concentration of 761.17 ± 1.8 µg/mL. Intriguingly, in vitro cytotoxicity assays against human breast cancer (MCF-7) cells revealed varying levels of cell viability at different extract concentrations, suggesting potential anticancer properties. Importantly, these ethyl acetate extracts did not display toxicity to L929 cells across the concentration range tested. Subsequently, we conducted in-silico molecular docking experiments utilizing Discovery Studio 4.0 against the c-Met kinase protein (hepatocyte growth factor; PDB ID: 1N0W). Among the various compounds assessed, 3,4-Dihydroxy-1,6-bis-(3-methoxy-phenyl)-hexa-2,4-diene-1,6-dione exhibited a notable binding energy of -9.1 kcal/mol, warranting further investigation into its potential anticancer properties, clinical applications, and broader pharmacological characteristics.

Facile synthesis of green engineered CuO/Cu2O-C nano heterostructures with the controlled Cu2O content for the photodegradation of crystal violet

Copper oxide/cuprous oxide and carbon heterostructured nanocomposites (CuO/Cu2O-C NCs) were fabricated using an agro-biomass wheatgrass extract (WGE), presenting an innovative, eco-friendly, and facile green synthetic approach. The CuO/Cu2O-C nanocomposites engineered using WGE were extensively characterized using UV–Vis, IR, XRD, DLS, XPS, SEM, TEM, BET, and TGA characterization techniques. The synthesized CuO/Cu2O-C NCs were crystalline with a monoclinic phase and an average crystallite size of 32 nm, as confirmed by XRD. Tauc plots were utilized to calculate the band gap energies (2.05 and 1.53 eV). The synthetic procedure is optimized, and the effect of plant extract in the controlled synthesis of Cu2O content in the CuO/Cu2O-C NCs was investigated. These green CuO/Cu2O-C NCs were tested for photocatalytic activity. A detailed kinetic study was conducted to degrade pathological effluent crystal violet (CV). The nanocomposite with a higher concentration of Cu2O is potentially a superior photocatalyst and demonstrated an excellent synergistic action, removing around 80 % of the crystal violet stain in visible light. Apart from photodegradation, these CuO/Cu2O-C NCs were good antioxidants and displayed good antibacterial activity against the gram-positive and gram-negative bacterial strains. The key highlight of this work is the low-cost disruptive engineering strategy for synthesizing frugal nanomaterials for multifaceted applications.

Iodine functionalized 2,5-dimethoxy-2,5-dihydrofuran (DHFI) crosslinked whey protein-derived carbon nanodots (WCND) for antibacterial application

Whey protein-derived carbon nanodots (WCND) were synthesized using the microwave irradiation method, and its amine-rich surface functionality was crosslinked with covalently bound Iodine functionalized 2,5-dimethoxy-2,5-dihydrofuran (DHFI) to produce WCND-DHFI. The physicochemical characterization of both WCND and WCND-DHFI was performed and compared to comprehend the consequence of iodination on the characteristics of WCND. The suitability of CND in biological environments was evaluated through in vitro cytocompatibility and Chorioallantoic Membrane (CAM) assay, as well as a hemocompatibility study. WCND-DHFI has shown enhanced cell viability against WCND. Further, the antibacterial properties of both CNDs were studied against both gram-positive and gram-negative bacterial strains, representing an enhancement in antibacterial activity after DHFI crosslinking. WCND-DHFI has depicted a stable and prominent bacteriostatic activity for up to 6 h for both strains of bacteria. WCND-DHFI has denoted a 99.996% and 99.999% loss of bacterial viability for gram-positive and negative strains, respectively. Novel surface functionalization portrays an improvement in antibacterial activity. Transmission and scanning electron microscopy represent the cell wall rupturing by the WCND-DHFI, resulting in bacterial death. The ROS-mediated bacteriostatic mechanism of WCND-DHFI has been explored through assessing lipid peroxidation and protein oxidation assay. Moreover, the oxidative damage of DNA also has been explored. WCND-DHFI is performing as a promising cytocompatible and hemocompatible material for antibacterial applications.

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications.

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound's structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 μg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets.

Exploring the antibacterial effects of Ocimum sanctum (O. sanctum) silver nanoparticles

The current study was undertaken to provide sustainable solutions to Erythromycin-resistant bacterial strains. Silver nanoparticles were produced using an environmentally friendly green synthesis process using Ocimum sanctum leaf extract. The synthesized Ocimum sanctum leaf extract silver nanoparticles were then examined using a variety of methods. In the UV-Vis spectrophotometer, the peak was observed at 398nm. Scanning electron microscopy (SEM) revealed the size of the nanoparticles to be between 24-44nm. The crystalline size of AgNPs was determined to be 12.02nm by X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy revealed the presence of functional groups like alcohols, phenols and carbonyl groups which provide better interaction and stability of the nanoparticles. Bioactive compounds of Ocimum sanctum leaves were found to be effective against both Gram-positive and Gram-negative bacterial strains as nanoparticles which is evident by having no inhibition against Bacillus Subtilis and E. coli in lower concentrations of 30μl and 50μl. On the other hand, Ocimum sanctum leaf extract AgNPs had a positive dose-dependent inhibition against all the strains. The Ocimum sanctum silver nanoparticles were effective against E. coli (Gram-negative), Staphylococcus aureus (1.9cm), Streptococcus mutans (1.7cm) and Bacillus Subtilis (Gram-positive). Thus, Ocimum sanctum Silver Nanoparticle-based drug delivery has proven to be an effective anti-bacterial treatment worth exploring specifically against Erythromycin-resistant strains.

Synthesis of curcuma longa doped cellulose grafted hydrogel for catalysis, bactericidial and insilico molecular docking analysis

Curcumin (diferuloylmethane), the primary curcuminoid in turmeric rhizome, has been acknowledged as a bioactive compound for numerous pharmacological activities. Nonetheless, the hydrophobic nature, rapid metabolism, and physicochemical and biological instability of this phenolic compound correspond to its poor bioavailability. So, recent scientific advances have found many components and strategies for enhancing the bioavailability of curcumin with the inclusion of biotechnology and nanotechnology to address its existing limitations. Therefore, In this study, copolymerized aqua-gel was synthesized by graft polymerization of poly-acrylic acid (P-AA) on cellulose nanocrystals (CNC), after that Curcuma longa (Cur) was incorporated as dopant (5, 10, 15, and 25 mg) in hydrogel (Cur/C-P) as a stabilizing agent for evaluation of bacterial potential and sewage treatment. The antioxidant tendency of 25 mg Cur/C-P was much higher (72.21 %) than other samples and displayed a catalytic activity of up to 93.89 % in acidic conditions and optimized bactericidal inclinations toward gram-positive bacterial strains. Furthermore, ligand binding was conducted against targeted protein enoyl-[acylcarrier-protein] reductase (FabI) enzyme to comprehend the putative mechanism of microbicidal action of CNC-PAA (CP), Cur/C-P, and curcumin. Our outcomes suggest that 25 mg Cur/C-P hydrogels are plausible sources for hybrid, multifunctional biological activity.

Antimicrobial agents based on new lipophilic alkyl (N-alkyl-N,N-dioctylammoniomethyl)phosphonates

(N-Alkyl-N,N-dioctylammoniomethyl)phosphonates were obtained by alkylation of amino phosphonate potassium salt with alkyl iodides or benzyl chloride. All synthesized compounds demonstrated high antibacterial and antifungal activity against Gram-positive bacterial strains B. cereus and S. aureus and were not active against Gram-negative strains Ps. aeruginosa. Some regularity connecting the structure of the obtained compounds with their antimicrobial action has been established.

Design, synthesis, biological evaluation, and bio-computational modeling of imidazo, thieno, pyrimidopyrimidine, pyrimidodiazepene, and motifs as antimicrobial agents

Abstract In the drug chemistry industry, synthesizing a talented exclusive series of aza-polyheterocyclic compounds was crucial. Aminopyrimidine nucleus reacted with two equivalents of benzaldehyde in the presence of KOH as a starting material to bring about imidazopyrimidine derivative, which experienced intermolecular cyclization using carbon disulfide, Br2/AcOH, and/or HNO2 to produce thiazole, thieno, and/or nitro pyrimidine derivative, respectively. Accordingly, the nucleus of Aminopyrimidine was prepared and used to develop the novel polyheterocyclic systems acylated with two moles of succinic anhydride to furnish the imidazolopyrimidine derivative. Benzylidene ethyl cyanoacetate and aminopyrimidine undergo (3 + 4) intermolecular cycloaddition 1,3 H shift followed by hydrolysis and after CO2 evolution provided diazepine derivative. The diazepine derivative was attained due to the cyclo-condensation of the starting material and acetylacetone. Moreover, the structure of the novel synthesized compound series was exploited and verified via spectroscopic approaches. The synthesized series were tested for antimicrobial activity against gram-positive and gram-negative bacterial strains and antifungal activity. The thienopyrimidine derivatives and diazepine exhibited unusual antimicrobial activity. Furthermore, the molecular docking studies confirmed the biological studies with Molecular Operating Environment and petro orisis molinspiration studies, which proved the activity of compounds 4, 5, 7, 10, 13, and 16.

Antibacterial Activity of Ethanolic Extracts of Terminalia coriacea (Roxb.) Wight and Arn. Leaves against Foodborne Pathogens

Pathogens spread on food items during the stages of storage, transit and processing. Thus, the eradication of these microorganisms holds significant importance. Ethanolic extract of Terminalia coriacea was used against Escherichia coli NCIM2134, Pseudomonas aeroginosa NCIM2037, Klebsiella pneumonia NCIM2706, Bacillus subtilis NCIM2920, Staphylococcus aureus NCIM5345 and Staphylococcus epidermidis NCIM5755 by disk diffusion and microdilution methods to evaluate the antibacterial activity. The ethanolic extract of Terminalia coriacea (Roxb.) leaves gave significant activity against all tested species of bacteria, which was compared to the standard disinfectant of 0.1% of commercial chlorhexidine. The inhibitions zones ranged from 6.45 ± 0.82 to 9.52 ± 0.30 for different bacterial strains. The minimum inhibitory concentration (MIC) was observed, ranging from 0.73 mg/mL to 1.35 mg/mL and the minimum bactericidal concentration (MBC) was observed, ranging from 0.73 mg/mL to 2.50 mg/mL. Based on the obtained results, it is suggested that the T. coriacea demonstrates antimicrobial properties against both Gram-positive and Gram-negative bacterial strains commonly encountered in food products. This plant extract can be further developed for the sanitizing of food items.

A 3D-printed multi-compartment device that enables dynamic PK/PD profiles of antibiotics.

Pathogens develop resistance to various drugs while under the selective pressure of antibiotics resulting in the emergence of bacterial strains that are resistant to multiple treatment options. Unfortunately, the resistance to antibiotics has also been accompanied by a reduction in the development of novel antibiotics to combat various pathogens. Current diagnostic tools, which are used in parts of the early developmental process of antibiotics, primarily consist of static susceptibility tests that do not resemble the pharmacokinetics of the therapy in vivo. Here, we designed and 3D-printed cubical inserts with membranes on two of the cube faces that allow diffusion of a molecule across two planes. These inserts are used with a 3D-printed device to create a two-compartment model to mimic the pharmacokinetics of a molecule in humans from multiple types of administration. Fluorescein was used to characterize the device and the diffusion of molecules from a flowing channel, through a membrane in the first plane (representing the primary compartment in vivo, or plasma), followed by measurement in the second compartment (that represents the interstitial fluid). The dynamic, two-compartment model was tested using both gram-positive and gram-negative bacterial strains in the secondary compartment. The ATP/OD600 (a measure of antibiotic activity)ofa kanamycin-resistant E. coli strain challenged with the antibiotic levofloxacin increased after reaching an effective concentration of the antibiotic at 2 h, equating to a secondary compartment concentration of 3.5 ± 1.3 µM levofloxacin. The ATP/OD600 of achloramphenicol-resistant B. subtilis strain challenged withthe antibiotic levofloxacin remained steady or increased slightly after reaching an effective concentration of the antibiotic. The earliest statistical difference was detected 3 h after the start of the PK curve, which corresponds with a secondary compartment concentration of 4.8 ± 1.8 µM levofloxacin. Our results demonstrate that a fabricated 2-compartment model (1) provides realistic PK values to those published from in vivo studies and (2) can be used to determine antibiotic pharmacodynamics.

Combinatorial Screening of Cationic Lipidoids Reveals How Molecular Conformation Affects Membrane-Targeting Antimicrobial Activity.

The search for next-generation antibacterial compounds that overcome the development of resistance can be facilitated by identifying how to target the cell membrane of bacteria. Understanding the key molecular features that enable interactions with lipids and lead to membrane disruption is therefore crucial. Here, we employ a library of lipid-like compounds (lipidoids) comprising modular structures with tunable hydrophobic and hydrophilic architecture to shed light on how the chemical functionality and molecular shape of synthetic amphiphilic compounds determine their activity against bacterial membranes. Synthesized from combinations of 8 different polyamines as headgroups and 13 acrylates as tails, 104 different lipidoids are tested for activity against a model Gram-positive bacterial strain (Bacillus subtilis). Results from the combinatorial screening assay show that lipidoids with the most potent antimicrobial properties (down to 2 μM) have intermediate tail hydrophobicity (i.e., c log P values between 3 and 4) and lower headgroup charge density (i.e., longer spacers between charged amines). However, the most important factor appeared to be the ability of a lipidoid to self-assemble into an inverse hexagonal liquid crystalline phase, as observed by small-angle X-ray scattering (SAXS) analysis. The lipidoids active at lowest concentrations, which induced the most significant membrane damage during propidium iodide (PI) permeabilization assays, were those that aggregated into highly curved inverse hexagonal liquid crystal phases. These observations suggest that the introduction of strong curvature stress into the membrane is one way to maximize membrane disruption and lipidoid antimicrobial activity. Lipidoids that demonstrated the ability to furnish this phase consisted of either (i) branched or linear headgroups with shorter linear tails or (ii) cyclic headgroups with 4 bulky nonlinear tails. On the contrary, lipidoids previously observed to adopt disc-like conformations that pack into bicontinuous cubic phases were significantly less effective against B. subtilis. The discovery of these structure-property relationships demonstrates that it is not simply a balance of hydrophobic and hydrophilic moieties that govern membrane-active antibacterial activity, but also their intrinsic curvature and collective behavior.

Synthesis of a novel Cu/DPA-MOF/OP/CS hydrogel with high capability in antimicrobial studies.

Today, with the indiscriminate use of antibiotics, we face the resistance of some bacterial strains against some antibiotics. Therefore, it is essential to report and synthesize new compounds with antimicrobial properties. A novel copper/dipicolinic acid-metal-organic framework cross-linked oxidized pectin and chitosan (Cu/DPA-MOF/OP/CS) hydrogel polymer was synthesized under environmental conditions with the controllable process, which uses biodegradable polymer compounds such as pectin and chitosan in its structure. The efficient physicochemical features of the synthesized Cu/DPA-MOF/OP/CS hydrogel using SEM, FT-IR, TGA, BET, XRD, and EDS/mapping were identified and confirmed. The newly synthesized Cu/DPA-MOF/OP/CS hydrogel showed activity against Gram-positive and Gram-negative bacterial strains and fungal species, and significant antibacterial and antifungal properties were observed. In antibacterial activity, the MIC against Gram-positive species was in the range of 16-128mg/mL, the MIC against Gram-negative species was in the range of 64-256mg/mL, and the MIC against fungal species was in the range of 128-512mg/mL. In antimicrobial evaluations, in addition to the MIC test, the MBC test, the MFC test, and the IZD test were performed, and the results were reported. The results were compared with commercial antibiotics in the market. Development of novel nanostructures based on hydrogel polymers with distinctive functionality can affect the performance of these nanostructures in different areas.

Iron Oxide Nanoparticles as Anti-Virulence Factors of Gram-positive and Gram-negative Bacteria

Background: Due to their extensive use in medical therapy, iron oxide nanoparticles have recently attracted the attention of researchers in the field of increasing multi-resistance properties in bacterial pathogens. Because iron oxide nanoparticles have a high specific surface area, they can interact with bacterial surface structures and exhibit significant antibacterial activity. Objective: The current work, determined the effect of a novel anti-virulence factor agent which was created from iron oxide nanoparticles against selected gram-positive and gram-negative variant bacterial strains that were isolated and identified from elderly Iraqi patients with urinary tract infections. Methods: Seven bacterial strains (three gram-positive and four gram-negative) were tested for their (biofilm, adhesion, and hemolysis) activity using the quantitative test-tube method, glass-slide method, and by determining the hemolysis ability of bacterial isolates against previously prepared RBC, respectively. The highest virulence factors formation bacterial isolates were chosen to determine the effect of Iron-oxide nanoparticles. Previously prepared and characterized Iron- oxide nanoparticles were used as anti- (biofilm, adhesion, and hemolysis) by using specific Bacterial-Fe3O4 NPs complex with different concentrations. The Results: All these bacteria expressed their virulence factors, the highest-level biofilm formation abilities were detected in Proteus mirabilis and Staphylococcus aureus, and the highest-level adhesion activity was observed in Enterococcus faecalis and Pseudomonas aeruginosa while the highest-level hemolysis activities on human RBC were determined in Micrococcus luteus and E. coli. The effects of (Fe3O4) nanoparticles against the highest virulence factors bacterial isolates shows an increases in the biofilm formation abilities of S. aureus and P. mirabilis as well as for standard bacterial strains the anti-biofilm formation ability of (Fe3 O4) NPs against gram-positive S. aureus, Proteus mirabilis, and standard gram-negative bacteria demonstrated an in-decrease biofilm formation ability of these bacteria effective at (5000 and 10000 µg/ml). The anti-adhesion ability of (Fe3 O4) NPs against gram-positive Enterococcus faecalis, and gram-negative Pseudomonas aeruginosa determined no effect on the adhesion abilities of gram-positive and negative bacteria atall concentrations (250, 400, 500, 750 and 1000µg/ml) Finally, the effect of different concentrations of iron oxide nanoparticles on the hemolysis ability of Micrococcus luteus and Escherichia coli on RBC was determined, the highest hemolysis inhibition level was estimated in 1000 µg/ml and the less inhibition in 500 µg/ml as compared with control.