Structure and ligand binding in the putative anti-microbial peptide transporter protein, YejA.

YejABEF is an ATP-binding cassette transporter that is implicated in the sensitivity of Escherichia coli to anti-microbial peptides, the best-characterized example being microcin C, a peptide-nucleotide antibiotic that targets aspartyl-tRNA synthetase. Here the structure of the extracellular solute binding protein, YejA, has been determined, revealing an oligopeptide-binding protein fold enclosing a ligand-binding pocket larger than those of other peptide-binding proteins of known structure. Prominent electron density in this cavity defines an undecapeptide sequence LGEPRYAFNFN, an observation that is confirmed by mass spectrometry. In the structure, the peptide interactions with the protein are mediated by main chain hydrogen bonds with the exception of Arg5 whose guanidinium side chain makes a set of defining polar interactions with four YejA residues. More detailed characterization of purified recombinant YejA, by a combination of ESI and MALDI-mass spectrometry as well as thermal shift assays, reveals a set of YejA complexes containing overlapping peptides 10-19 residues in length. All contain the sequence LGEPRYAFN. Curiously, these peptides correspond to residues 8-26 of the mature YejA protein, which belong to a unique N-terminal extension that distinguishes YejA from other cluster C oligopeptide binding proteins of known structure. This 35-residue extension is well-ordered and packs across the surface of the protein. The undecapeptide ligand occupies only a fraction of the enclosed pocket volume suggesting the possibility that much larger peptides or peptide conjugates could be accommodated, though thermal shift assays of YejA binding to antimicrobial peptides and peptides unrelated to LGEPRYAFNFN have not provided evidence of binding. While the physiological significance of this 'auto-binding' is not clear, the experimental data suggest that it is not an artefact of the crystallization process and that it may have a function in the sensing of periplasmic or membrane stress.

Green and environmentally friendly synthesis of silver nanoparticles with antibacterial properties from some medicinal plants.

Recently there have been a variety of methods to synthesize silver nanoparticles, among which the biosynthesis method is more noticeable due to features like being eco-friendly, simple, and cost-efficient. The present study aims for the green synthesis of silver nanoparticles from the extract of the three plants A. wilhelmsi, M. chamomilla, and C. longa; moreover, it pledges to measure the antibacterial activity against some variants causing a skin rash. The morphology and size of the synthesized silver nanoparticles were evaluated by UV.vis, XRD, SEM, and FTIR analyses. Then results showed a color alteration from light yellow to dark brown and the formation of silver nanoparticles. The absorption peak with the wavelength of approximately 450 nm resulting from the Spectrophotometry analysis confirmed the synthesis of silver nanoparticles. The presence of strong and wide peaks in FTIR indicated the presence of OH groups. The SEM results showed that most synthesized nanoparticles had a spherical angular structure and their size was about 10 to 20 nm. The highest inhibition power was demonstrated by silver nanoparticles synthesized from the extract combined from all three species against Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis (23 mm) which had a performance far more powerful than the extract. Thus, it can be understood that the nanoparticles synthesized from these three species can act as potential environment-friendly alternatives to inhibit some variations causing skin disorders; an issue that calls for further clinical studies.

The role of ion dissolution in metal and metal oxide surface inactivation of SARS-CoV-2.

Anti-viral surface coatings are under development to prevent viral fomite transmission from high-traffic touch surfaces in public spaces. Copper's anti-viral properties have been widely documented, but the anti-viral mechanism of copper surfaces is not fully understood. We screened a series of metal and metal oxide surfaces for anti-viral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19). Copper and copper oxide surfaces exhibited superior anti-SARS-CoV-2 activity; however, the level of anti-viral activity was dependent on the composition of the carrier solution used to deliver virus inoculum. We demonstrate that copper ions released into solution from test surfaces can mediate virus inactivation, indicating a copper ion dissolution-dependent anti-viral mechanism. The level of anti-viral activity is, however, not dependent on the amount of copper ions released into solution per se. Instead, our findings suggest that degree of virus inactivation is dependent on copper ion complexation with other biomolecules (e.g., proteins/metabolites) in the virus carrier solution that compete with viral components. Although using tissue culture-derived virus inoculum is experimentally convenient to evaluate the anti-viral activity of copper-derived test surfaces, we propose that the high organic content of tissue culture medium reduces the availability of "uncomplexed" copper ions to interact with the virus, negatively affecting virus inactivation and hence surface anti-viral performance. We propose that laboratory anti-viral surface testing should include virus delivered in a physiologically relevant carrier solution (saliva or nasal secretions when testing respiratory viruses) to accurately predict real-life surface anti-viral performance when deployed in public spaces.IMPORTANCEThe purpose of evaluating the anti-viral activity of test surfaces in the laboratory is to identify surfaces that will perform efficiently in preventing fomite transmission when deployed on high-traffic touch surfaces in public spaces. The conventional method in laboratory testing is to use tissue culture-derived virus inoculum; however, this study demonstrates that anti-viral performance of test copper-containing surfaces is dependent on the composition of the carrier solution in which the virus inoculum is delivered to test surfaces. Therefore, we recommend that laboratory surface testing should include virus delivered in a physiologically relevant carrier solution to accurately predict real-life test surface performance in public spaces. Understanding the mechanism of virus inactivation is key to future rational design of improved anti-viral surfaces. Here, we demonstrate that release of copper ions from copper surfaces into small liquid droplets containing SARS-CoV-2 is a mechanism by which the virus that causes COVID-19 can be inactivated.

Function analysis and characterisation of a novel chitinase, MdCht9, in Musca domestica.

Insect chitinases have been proposed as potential targets for pest control. In this work, a novel group IV chitinase gene, MdCht9, from Musca domestica was found to have multiple functions in the physiological activity, including chitin regulation, development and antifungal immunity. The MdCht9 gene was cloned and sequenced, its phylogeny was analysed and its expression was determined in normal and 20E treated larvae. Subsequently, RNA interference (RNAi)-mediated MdCht9 knockdown was performed, followed by biochemical assays, morphological observations and transcriptome analysis. Finally, the recombinant protein MdCht9 (rMdCht9) was purified and tested for anti-microbial activity and enzyme characteristics. The results showed that MdCht9 consists of three domains, highly expressed in a larval salivary gland. RNAi silencing of MdCht9 resulted in significant down-regulation of chitin content and expression of 15 chitin-binding protein (CBP) genes, implying a new insight that MdCht9 might regulate chitin content by influencing the expression of CBPs. In addition, more than half of the lethality and partial wing deformity appeared due to the dsMdCht9 treatment. In addition, the rMdCht9 exhibited anti-microbial activity towards Candida albicans (fungus) but not towards Escherichia coli (G-) or Staphylococcus aureus (G+). Our work expands on previous studies of chitinase while providing a potential target for pest management.

Exosome-like nanoparticles from Mulberry bark prevent DSS-induced colitis via the AhR/COPS8 pathway.

Bark protects the tree against environmental insults. Here, we analyzed whether this defensive strategy could be utilized to broadly enhance protection against colitis. As a proof of concept, we show that exosome-like nanoparticles (MBELNs) derived from edible mulberry bark confer protection against colitis in a mouse model by promoting heat shock protein family A (Hsp70) member 8 (HSPA8)-mediated activation of the AhR signaling pathway. Activation of this pathway in intestinal epithelial cells leads to the induction of COP9 Constitutive Photomorphogenic Homolog Subunit 8 (COPS8). Utilizing a gut epithelium-specific knockout of COPS8, we demonstrate that COPS8 acts downstream of the AhR pathway and is required for the protective effect of MBELNs by inducing an array of anti-microbial peptides. Our results indicate that MBELNs represent an undescribed mode of inter-kingdom communication in the mammalian intestine through an AhR-COPS8-mediated anti-inflammatory pathway. These data suggest that inflammatory pathways in a microbiota-enriched intestinal environment are regulated by COPS8 and that edible plant-derived ELNs may hold the potential as new agents for the prevention and treatment of gut-related inflammatory disease.

Antarctic marine sediment as a source of filamentous fungi-derived antimicrobial and antitumor compounds of pharmaceutical interest.

Antarctica harbors a microbial diversity still poorly explored and of inestimable biotechnological value. Cold-adapted microorganisms can produce a diverse range of metabolites stable at low temperatures, making these compounds industrially interesting for biotechnological use. The present work investigated the biotechnological potential for antimicrobial and antitumor activity of filamentous fungi and bacteria isolated from marine sediment samples collected at Deception Island, Antarctica. A total of 89 microbial isolates were recovered from marine sediments and submitted to an initial screening for L-glutaminase with antitumoral activity and for antimicrobial metabolites. The isolates Pseudogymnoascus sp. FDG01, Pseudogymnoascus sp. FDG02, and Penicillium sp. FAD33 showed potential antiproliferative action against human pancreatic carcinoma cells while showing no toxic effect on non-tumor cells. The microbial extracts from unidentified three bacteria and four filamentous fungi showed antibacterial activity against at least one tested pathogenic bacterial strain. The isolate FDG01 inhibited four bacterial species, while the isolate FDG01 was active against Micrococcus luteus in the minimal inhibitory concentration of 0.015625 µg mL -1. The results pave the way for further optimization of enzyme production and characterization of enzymes and metabolites found and reaffirm Antarctic marine environments as a wealthy source of compounds potentially applicable in the healthcare and pharmaceutical industry.

A novel metabolite of Streptomyces coeruleorubidus exhibits antibacterial activity against Streptococcus agalactiae through modulation of physiological performance, inflammatory cytokines, apoptosis, and oxidative stress-correlated gene expressions in Nile tilapia (Oreochromis niloticus).

Using the unique structures found in natural materials to produce new antibacterial drugs is crucial. Actinobacteria is well-known for its ability to produce naturally occurring chemicals with a variety of structural features that can be used as weapons against infectious bacteria. In the present study, the Streptomyces coeruleorubidus metabolites were characterized and their efficacy in suppressing Streptococcus agalactiae growth was carried out both in vitro and in vivo. The metabolites of S. coeruleorubidus were purified and identified as octasiloxane-hexadecamethyl (OHM). In vivo antibacterial activity of OHM revealed an inhibitory minimum concentration value of 0.5 µg/ml against S. agalactiae and induced ultrastructural cell changes revealed by scanning electron microscope. The safe concentration of OHM was determined as 0.8 mg/L for Nile tilapia. Four in vivo treatments were treated with 0 and 0.8 mg/L OHM and with or without challenge by S. agalactiae (1 × 107 CFU/mL) named control, OHM, S. agalactiae, and S. agalactiae + OHM groups. The OHM treatment improved the survival of Nile tilapia by 33.33% than S. agalactiae challenge group. Waterborne OHM treatment significantly mitigated the deleterious effects of S. agalactiae on hematological, hepato-renal functions, stress indicators, and antioxidant balance. OHM significantly alleviated nitric oxide levels, complement 3, IgM, and lysozyme activity, downregulation of liver antioxidant genes expression in S. agalactiae group. Furthermore, the addition of OHM to challenged fish with S. agalactiae-significantly reversed dramatic negative regulation of inflammatory, apoptosis, and immune related gene expression (caspase-3, bax, pcna, tnf-α, ifn-γ, il-8 il-1ß, il-10, tgf-ß, and bcl-2 in the Nile tilapia spleen. Additionally, the damaged hepatic and splenic structure induced by bacterial infection was restored with OHM treatment. Finally, S. coeruleorubidus metabolites (mainly OHM) revealed in vitro and in vivo antibacterial activity and showed alleviated effects on the physiological status of S. agalactiae infected tilapia.

Comparative evaluation of antimicrobial activity of spinel structured transition metal ferrites supported on reduced graphene oxide against pathogenic strains of bacteria and fungi.

One of the global challenges for living things is to provide pollution and harmful microbes-free environment. In this study, magnetically retrievable spinel-structured manganese zinc ferrite (Mn0.5Zn0.5Fe2O4) (MZF) was synthesized by a facile solvothermal method. Further, the MZF with different weight percentages (10 wt%, 50 wt%, and 80 wt%) were supported on reduced graphene oxide (rGO). The phase purity and morphology of MZF and MZF/rGO nanocomposite were confirmed by x-ray diffraction technique and scanning electron microscopy, respectively. The Fourier transform infrared spectroscopy, Raman, UV-visible spectroscopy, and thermogravimetric analyses of the as-synthesized nanocomposites were examined for the detection of various chemical groups, band gap, and thermal properties, respectively. The MZF/rGO nanocomposite exhibited significant antibacterial and antifungal activity againstEggerthella lenta, Enterococcus faecalis, Klebsiella pneumonia, Pseudomonas aeruginosa,andCandida albicanscompared to bare MZF and rGO. The high surface area of rGO plays a crucible role in antimicrobial analysis. Additionally, the antibacterial and antifungal activity is compared by synthesizing various metal ferrites such as MnFe2O4, ZnFe2O4, and Fe3O4. The 50 wt% MZF/rGO nanocomposite exhibits significantly high antibacterial activity. However, 10 wt% MZF/rGO nanocomposite shows good antifungal activity than Fe3O4, MnFe2O4, ZnFe2O4, MnZnFe2O4, 50 wt%, and 80 wt% MZF/rGO nanocomposites. These findings suggest that the prepared ferrite nanocomposites hold promise for microbial inhibition.

Curcumin is effective in managing oral inflammation: An in vitro study.

BACKGROUND: Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti-inflammatory and antioxidant properties, this study focuses on the potential of a curcumin-based oral gel in safely managing oral inflammatory conditions. METHODS: This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin-based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis. RESULTS: LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin-based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line-specific manner. The curcumin-based oral gel showed significant antimicrobial efficacy against C. albicans and S. mutans, but was ineffective against P. gingivalis. CONCLUSION: This study demonstrates the potential of the curcumin-based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical-based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare.

Recent developments on the synthesis of biologically active glycohybrids.

The exploration of hybridization emerges as a potent tool in advancing drug discovery research, with a significant emphasis on carbohydrate-containing hybrid scaffolds. Evidence indicates that linking carbohydrate molecules to privileged bioactive scaffolds enhances the bioactivity of drug molecules. This synergy results in a diverse range of activities, making carbohydrate scaffolds pivotal for synthesizing compound libraries with significant functional and structural diversity. Beyond their synthesis utility, these scaffolds offer applications in screening bioactive molecules, presenting alternative avenues for drug development. This comprehensive review spanning 2015 to 2023 focuses on synthesized glycohybrid molecules, revealing their bioactivity in areas such as anti-microbial, anti-cancer, anti-diabetic, anti-inflammatory activities, enzyme inhibition and pesticides. Numerous novel glycohybrids surpass positive control drugs in biological activity. This focused study not only highlights the diverse bioactivities of glycohybrids but also underscores their promising role in innovative drug development strategies.

Synthesis and characterization of Pyrus communis fruit extract synthesized ZnO NPs and assessed their anti-diabetic and anti-microbial potential.

The fruit Pyrus communis, owing to its presence of phenolics and flavonoids, was chosen for its nanoparticle's reducing and stabilizing properties. Furthermore, the zinc metal may be nano-absorbed by the human body. As a result, the study involves synthesizing zinc oxide nanoparticles (ZnO NPs) from P. communis fruit extract using the green method. The synthesized nanoparticle was examined with a UV-visible spectrophotometer, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Dynamic Light Scattering (DLS). When absorption studies were performed with a UV-visible spectrophotometer, the nanoparticle exhibited a blue shift. The FTIR spectrum revealed the molecular groups present in both the fruit extract and metal. In the SEM analysis, the ZnO NPs appeared as spherical particles, agglomerated together, and of nano-size. The larger size of the ZnO NPs in DLS can be attributed to their ability to absorb water. After characterization, nanoparticles were tested for anti-diabetic (α-amylase and yeast glucose uptake activity) and anti-microbial properties. The α-amylase inhibition percentage was 46.46 ± 0.15% for 100 µg/mL, which was comparable to the acarbose inhibition percentage of 50.58 ± 0.67% at the same concentration. The yeast glucose uptake activity was 64.24 ± 0.80% at 20 mM glucose concentration, which was comparable to the standard of 78.03 ± 0.80. The nanoparticle was more effective against Gram-negative bacteria Shigella sp. and Salmonella typhi than against Gram-positive bacteria Bacillus cereus and Streptococcus pneumoniae.

Marine Streptomyces-Derived Novel Alkaloids Discovered in the Past Decade.

Natural alkaloids originating from actinomycetes and synthetic derivatives have always been among the important suppliers of small-molecule drugs. Among their biological sources, Streptomyces is the highest and most extensively researched genus. Marine-derived Streptomyces strains harbor unconventional metabolic pathways and have been demonstrated to be efficient producers of biologically active alkaloids; more than 60% of these compounds exhibit valuable activity such as antibacterial, antitumor, anti-inflammatory activities. This review comprehensively summarizes novel alkaloids produced by marine Streptomyces discovered in the past decade, focusing on their structural features, biological activity, and pharmacological mechanisms. Future perspectives on the discovery and development of novel alkaloids from marine Streptomyces are also provided.

Synthesis, Characterization, DNA Binding, Biological Significance, and Molecular Docking Approaches of a Palladium(II) Complex with Ciprofloxacin for More Efficient Therapy.

To evaluate the biotransformation and the mechanism of binding as well as the biological impact of metal-based- drugs involving Pd(II), known to have high potency and low toxicity for use as anticancer therapeutics, in the present study, a newly synthesized palladium (II) complex, [Pd(CPF)(OH2)2]2+ (where CPF is ciprofloxacin), has been synthesized and characterized and thoroughly evaluated for its antimicrobial properties. The interaction of the diaqua complex with CT-DNA and BSA was studied through various techniques, including UV-vis spectroscopy, thermal denaturation, viscometry, gel electrophoresis, ethanol precipitation, and molecular docking studies. The results indicate that the complex exhibits a robust binding interaction with CT-DNA, possibly via minor groove binding and (or) electrostatic interactions. Furthermore, the complex displays good binding affinity towards BSA, indicating its potential as a target for DNA and BSA in biological media. The invitro cytotoxicity assay reveals that this complex can be classified as a promising cell growth inhibitor against MCF-7, HT-29, and A549. Thus, this newly synthesized palladium (II) complex is a promising candidate for further exploration as a potential anticancer therapeutic.

Antimicrobial Potential of Pomegranate and Lemon Extracts Alone or in Combination with Antibiotics against Pathogens.

Amidst the growing concern of antimicrobial resistance as a significant health challenge, research has emerged, focusing on elucidating the antimicrobial potential of polyphenol-rich extracts to reduce reliance on antibiotics. Previous studies explored the antifungal effects of extracts as potential alternatives to conventional therapeutic strategies. We aimed to assess the antibacterial and antifungal effects of standardised pomegranate extract (PE) and lemon extract (LE) using a range of Gram-negative and Gram-positive bacteria and two yeast species. Additionally, we assessed the antimicrobial activities of common antibiotics (Ciprofloxacin, Imipenem, Gentamicin, and Ceftazidime), either alone or in combination with extracts, against Staphylococcus aureus and Escherichia coli. PE displayed substantial antibacterial (primarily bactericidal) and antifungal effects against most pathogens, while LE exhibited antibacterial (mostly bacteriostatic) and antifungal properties to a lesser extent. When compared with antibiotics, PE showed a greater zone of inhibition (ZOI) than Ciprofloxacin and Ceftazidime (p < 0.01) and comparable ZOI to Gentamicin (p = 0.4) against Staphylococcus aureus. However, combinations of either PE or LE with antibiotics exhibited either neutral or antagonistic effects on antibiotic activity against Staphylococcus aureus and Escherichia coli. These findings contribute to the existing evidence regarding the antimicrobial effects of PE and LE. They add to the body of research suggesting that polyphenols exert both antagonistic and synergistic effects in antimicrobial activity. This highlights the importance of identifying optimal polyphenol concentrations that can enhance antibiotic activity and reduce antibiotic resistance. Further in vivo studies, starting with animal trials and progressing to human trials, may potentially lead to recommendation of these extracts for therapeutic use.

Physicochemical Properties and Biological Activities of Quinoa Polysaccharides.

Quinoa, known as the "golden grain" for its high nutritional value, has polysaccharides as one of its sources of important nutrients. However, the biological functions of quinoa polysaccharides remain understudied. In this study, two crude polysaccharide extracts of quinoa (Q-40 and Q-60) were obtained through sequential precipitation with 40% and 60% ethanol, with purities of 58.29% (HPLC) and 62.15% (HPLC) and a protein content of 8.27% and 9.60%, respectively. Monosaccharide analysis revealed that Q-40 contained glucose (Glc), galacturonic acid (GalA), and arabinose (Ara) in a molar ratio of 0.967:0.027:0.006. Q-60 was composed of xylose (xyl), arabinose (Ara), galactose, and galacturonic acid (GalA) with a molar ratio of 0.889:0.036:0.034:0.020. The average molecular weight of Q-40 ranged from 47,484 to 626,488 Da, while Q-60 showed a range of 10,025 to 47,990 Da. Rheological experiments showed that Q-40 exhibited higher viscosity, while Q-60 demonstrated more elastic properties. Remarkably, Q-60 showed potent antioxidant abilities, with scavenging rates of 98.49% for DPPH and 57.5% for ABTS. Antibacterial experiments using the microdilution method revealed that Q-40 inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), while Q-60 specifically inhibited MRSA. At lower concentrations, both polysaccharides inhibited MDA (MD Anderson Cancer Center) cell proliferation, but at higher concentrations, they promoted proliferation. Similar proliferation-promoting effects were observed in HepG2 cells. The research provides important information in the application of quinoa in the food and functional food industries.

Discovery of Potential Anti-Microbial Molecules and Spectrum Correlation Effect of Ardisia crenata Sims via High-Performance Liquid Chromatography Fingerprints and Molecular Docking.

Ardisia crenata Sims, an important ethnic medicine, is recorded in the Chinese Pharmacopoeia for treating laryngeal diseases and upper respiratory tract infections. This study aimed to evaluate the antimicrobial effect of extracts and potential antimicrobial compounds of A. crenata Sims. It was found that the roots of A. crenata Sims have a potential inhibitory effect on Candida albicans and Aspergillus flavus, with MICs of 1.56 mg/mL and 0.39 mg/mL, and the leaves of A. crenata Sims have a potential inhibitory effect on Pseudomonas aeruginosa and Staphylococcus aureus, with MICs of 3.12 mg/mL and 6.77 mg/mL, respectively. Meanwhile, five compounds including one catechin and four bergenins were obtained from roots. These components were identified on the fingerprint spectrum, representing chromatographic peaks 16, 21, 22, 23, and 25, respectively. Among these, 11-ß-d-glucopyranosyl-bergenin and (-)-gallocatechin showed potential inhibition for Staphylococcus aureus and Pseudomonas aeruginosa with MIC of 0.26 and 0.33 mg/mL, respectively. The roots, stems, and leaves of A. crenata Sims are very similar in chemical composition, with large differences in content. Principal component analysis (PCA) and Hierarchical cluster analysis (HCA) showed that 16 batches of A. crenata Sims could be divided into four main production areas: Guizhou, Jiangsu, Guangxi, and Jiangxi. Furthermore, molecular docking results showed that 11-ß-d-glucopyranosyl-bergenin had a better affinity for Casein lytic proteinase P (ClpP), and (-)-gallocatechin possessed a strong affinity for LasA hydrolysis protease and LasB elastase. These findings suggest catechin and bergenins from A. crenata Sims can be used as antimicrobial activity molecules.

Stereoselective Asymmetric Syntheses of Molecules with a 4,5-Dihydro-1H-[1,2,4]-Triazoline Core Possessing an Acetylated Carbohydrate Appendage: Crystal Structure, Spectroscopy, and Pharmacology.

A new series of chiral 4,5-dihydro-1H-[1,2,4]-triazoline molecules, featuring a ß-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition reaction between various hydrazonyl chlorides and carbohydrate Schiff bases. The isolated enantiopure triazolines (8a-j) were identified through high-resolution mass spectrometry (HRMS) and vibrational spectroscopy. Subsequently, their solution structures were elucidated through NMR spectroscopic techniques. Single-crystal X-ray analysis of derivative 8b provided definitive evidence for the 3-D structure of this compound and revealed important intermolecular forces in the crystal lattice. Moreover, it confirmed the (S)-configuration at the newly generated stereo-center. Selected target compounds were investigated for anti-tumor activity in 60 cancer cell lines, with derivative 8c showing the highest potency, particularly against leukemia. Additionally, substituent-dependent anti-fungal and anti-bacterial behavior was observed.

Engineering Whole-Cell Biosensors for Enhanced Detection of Environmental Antibiotics Using a Synthetic Biology Approach.

Bacterial Two component systems have evolved with many intricate sensory apparatuses for external stimuli like light, temperature, oxygen, pH and chemical compounds. Recent studies have shown the potential of two-component regulatory systems (TCSs) of bacteria in creating synthetic regulatory circuits for several applications. Antimicrobial resistance is increasing globally in both developing and developed countries and it is one of the foremost global threats to public health. The resistance level to a broad spectrum of antibiotics is rising every year by 5-10%. In this context, TCSs controlling microbial physiology at the transcriptional level could be an appropriate candidate for monitoring the antibiotics present in the environment. This review provided a wide opportunity to gain knowledge about the TCSs available in diverse species to sense the antibiotics. Further, this review explored the EMeRALD (Engineered Modularized Receptors Activated via Ligand-induced Dimerization) based biosensors to repurpose the sensing modules from the microbial TCSs using the synthetic biology approach.

Comparing antimicrobial resistant genes and phenotypes across multiple sequencing platforms and assays for Enterobacterales clinical isolates.

INTRODUCTION: Whole genome sequencing (WGS) of bacterial isolates can be used to identify antimicrobial resistance (AMR) genes. Previous studies have shown that genotype-based AMR has variable accuracy for predicting carbapenem resistance in carbapenem-resistant Enterobacterales (CRE); however, the majority of these studies used short-read platforms (e.g. Illumina) to generate sequence data. In this study, our objective was to determine whether Oxford Nanopore Technologies (ONT) long-read WGS would improve detection of carbapenem AMR genes with respect to short-read only WGS for nine clinical CRE samples. We measured the minimum inhibitory breakpoint (MIC) using two phenotype assays (MicroScan and ETEST) for six antibiotics, including two carbapenems (meropenem and ertapenem) and four non-carbapenems (gentamicin, ciprofloxacin, cefepime, and trimethoprim/sulfamethoxazole). We generated short-read data using the Illumina NextSeq and long-read data using the ONT MinION. Four assembly methods were compared: ONT-only assembly; ONT-only assembly plus short-read polish; ONT + short-read hybrid assembly plus short-read polish; short-read only assembly. RESULTS: Consistent with previous studies, our results suggest that the hybrid assembly produced the highest quality results as measured by gene completeness and contig circularization. However, ONT-only methods had minimal impact on the detection of AMR genes and plasmids compared to short-read methods, although, notably, differences in gene copy number differed between methods. All four assembly methods showed identical presence/absence of the blaKPC-2 carbapenemase gene for all samples. The two phenotype assays showed 100% concordant results for the non-carbapenems, but only 65% concordance for the two carbapenems. The presence/absence of AMR genes was 100% concordant with AMR phenotypes for all four non-carbapenem drugs, although only 22%-50% sensitivity for the carbapenems. CONCLUSIONS: Overall, these findings suggest that the lack of complete correspondence between CRE AMR genotype and phenotype for carbapenems, while concerning, is independent of sequencing platform/assembly method.

Methyl gallate: Review of pharmacological activity.

Methyl gallate (MG) is a polyphenolic compound widely found in natural plants. MG has been shown to have a variety of biological functions, including anti-tumor, anti-inflammatory, anti-oxidant, neuroprotective, hepatoprotective and anti-microbial activities, and has broad research and development prospects. A total of 88 articles related to MG were searched using the PubMed, Science Direct, and Google Scholar databases, systematically investigating the pharmacological activity and molecular mechanisms of MG. There were no restrictions on the publication years, and the last search was conducted on June 5, 2023. MG can exert pharmacological effects through multiple pathways and targets, such as PI3K/Akt, ERK1/2, Caspase, AMPK/NF-κB, Wnt/ß-catenin, TLR4/NF-κB, MAPK, p53, NLRP3, ROS, EMT. According to the literature, MG has the potential to be a prospective adjuvant for anticancer therapy and deserves further study.