E-CLEAP: An ensemble learning model for efficient and accurate identification of antimicrobial peptides.

With the increasing problem of antimicrobial drug resistance, the search for new antimicrobial agents has become a crucial task in the field of medicine. Antimicrobial peptides, as a class of naturally occurring antimicrobial agents, possess broad-spectrum antimicrobial activity and lower risk of resistance development. However, traditional screening methods for antimicrobial peptides are inefficient, necessitating the development of an efficient screening model. In this study, we aimed to develop an ensemble learning model for the identification of antimicrobial peptides, named E-CLEAP, based on the Multilayer Perceptron Classifier (MLP Classifier). By considering multiple features, including amino acid composition (AAC) and pseudo amino acid composition (PseAAC) of antimicrobial peptides, we aimed to improve the accuracy and generalization ability of the identification process. To validate the superiority of our model, we employed five-fold cross-validation and compared it with other commonly used methods for antimicrobial peptide identification. In the experimental results on an independent test set, E-CLEAP achieved accuracies of 97.33% and 84% for the AAC and PseAAC features, respectively. The results demonstrated that our model outperformed other methods in all evaluation metrics. The findings of this study highlight the potential of the E-CLEAP model in enhancing the efficiency and accuracy of antimicrobial peptide screening, which holds significant implications for drug development, disease treatment, and biotechnology advancement. Future research can further optimize the model by incorporating additional features and information, as well as validating its reliability on larger datasets and in real-world environments. The source code and all datasets are publicly available at https://github.com/Wangsicheng52/E-CLEAP.

An In Vitro Study on the Cytotoxic, Antioxidant, and Antimicrobial Properties of Yamogenin-A Plant Steroidal Saponin and Evaluation of Its Mechanism of Action in Gastric Cancer Cells.

Yamogenin is a steroidal saponin occurring in plant species such as Asparagus officinalis, Dioscorea collettii, Trigonella foenum-graecum, and Agave sp. In this study, we evaluated in vitro cytotoxic, antioxidant, and antimicrobial properties of yamogenin. The cytotoxic activity was estimated on human colon cancer HCT116, gastric cancer AGS, squamous carcinoma UM-SCC-6 cells, and human normal fibroblasts with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The amount of apoptotic and dead AGS cells after treatment with yamogenin was estimated with flow cytometry. Also, in yamogenin-treated AGS cells we investigated the reactive oxygen species (ROS) production, mitochondrial membrane depolarization, activity level of caspase-8 and -9, and gene expression at mRNA level with flow cytometry, luminometry, and RT-PCR, respectively. The antioxidant properties of yamogenin were assessed with DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. The antimicrobial potential of the compound was estimated on Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Helicobacter pylori, Campylobacter coli, Campylobacter jejuni, Listeria monocytogenes, Lactobacillus paracasei, and Lactobacillus acidophilus bacteria strains. Yamogenin showed the strongest cytotoxic effect on AGS cells (IC50 18.50 ± 1.24 µg/mL) among the tested cell lines. This effect was significantly stronger in combinations of yamogenin with oxaliplatin or capecitabine than for the single compounds. Furthermore, yamogenin induced ROS production, depolarized mitochondrial membrane, and increased the activity level of caspase-8 and -9 in AGS cells. RT-PCR analysis revealed that this sapogenin strongly up-regulated TNFRSF25 expression at the mRNA level. These results indicate that yamogenin induced cell death via the extrinsic and intrinsic way of apoptosis. Antioxidant study showed that yamogenin had moderate in vitro potential (IC50 704.7 ± 5.9 µg/mL in DPPH and 631.09 ± 3.51 µg/mL in ABTS assay) as well as the inhibition of protein denaturation properties (with IC50 1421.92 ± 6.06 µg/mL). Antimicrobial test revealed a weak effect of yamogenin on bacteria strains, the strongest one being against S. aureus (with MIC value of 350 µg/mL). In conclusion, yamogenin may be a potential candidate for the treatment and prevention of gastric cancers.

Advances in the Synthesis of Biologically Active Quaternary Ammonium Compounds.

This review provides a comprehensive overview of recent advancements in the design and synthesis of biologically active quaternary ammonium compounds (QACs). The covered scope extends beyond commonly reviewed antimicrobial derivatives to include synthetic agents with antifungal, anticancer, and antiviral properties. Additionally, this review highlights examples of quaternary ammonium compounds exhibiting activity against protozoa and herbicidal effects, as well as analgesic and anesthetic derivatives. The article also embraces the quaternary-ammonium-containing cholinesterase inhibitors and muscle relaxants. QACs, marked by their inherent permanent charge, also find widespread usage across diverse domains such as fabric softeners, hair conditioners, detergents, and disinfectants. The effectiveness of QACs hinges greatly on finding the right equilibrium between hydrophilicity and lipophilicity. The ideal length of the alkyl chain varies according to the unique structure of each QAC and its biological settings. It is expected that this review will provide comprehensive data for medicinal and industrial chemists to design and develop novel QAC-based products.

Therapeutic Potential of Nanocarrier Mediated Delivery of Peptides for Wound Healing: Current Status, Challenges and Future Prospective.

Wound healing presents a complex physiological process that involves a sequence of events orchestrated by various cellular and molecular mechanisms. In recent years, there has been growing interest in leveraging nanomaterials and peptides to enhance wound healing outcomes. Nanocarriers offer unique properties such as high surface area-to-volume ratio, tunable physicochemical characteristics, and the ability to deliver therapeutic agents in a controlled manner. Similarly, peptides, with their diverse biological activities and low immunogenicity, hold great promise as therapeutics in wound healing applications. In this review, authors explore the potential of peptides as bioactive components in wound healing formulations, focusing on their antimicrobial, anti-inflammatory, and pro-regenerative properties. Despite the significant progress made in this field, several challenges remain, including the need for standardized characterization methods, optimization of biocompatibility and safety profiles, and translation from bench to bedside. Furthermore, developing multifunctional nanomaterial-peptide hybrid systems represents promising avenues for future research. Overall, the integration of nanomaterials made up of natural or synthetic polymers with peptide-based formulations holds tremendous therapeutic potential in advancing the field of wound healing and improving clinical outcomes for patients with acute and chronic wounds.

Codetermination of antimicrobial agents in rabbit tear fluid using LC-MS/MS assay: Insights into ocular pharmacokinetic study.

Managing ocular microbial infections typically requires pharmacotherapy using antibiotic eye drops, such as moxifloxacin hydrochloride (MFX), combined with an antifungal agent like amphotericin B (AB). We carried out and validated an LC-MS/MS assay to quantify these compounds in rabbit tear fluid in order to look into the pharmacokinetics of these two drugs. We employed a protein precipitation technique for the extraction of drugs under examination. A Waters Symmetry C18 column was used to separate the analytes and internal standard. The composition of the mobile phase was like (A) 0.1% v/v formic acid in water and (B) methanol. The detection of MFX and AB was accomplished through the utilization of positive ion electrospray ionization under multiple reaction monitoring mode. The linearity curves for both analytes exhibited an acceptable trendline across a concentration range of 2.34-300 ng/mL for MFX and 7.81-1000 ng/mL for AB in surrogate rabbit tear fluid. The lower limit of quantitation for MFX was 2.34 ng/mL, while for AB, it was 7.81 ng/mL. The approach was strictly validated, encompassing tests of selectivity, linearity (with r2 > 0.99), precision, accuracy, matrix effects, and stability. Consequently, we employed this method to evaluate the pharmacokinetics profiles of MFX and AB in rabbit tear fluid following single topical doses.

Nanocomposites used in the treatment of skin lesions: a scoping review.

OBJECTIVE: To map the nanocomposites used in the treatment of skin lesions. METHOD: A scoping review, according to the Joanna Briggs Institute methodology, carried out on eight databases, a list of references and Google Scholar to answer the question: "Which nanocomposites are used as a cover for the treatment of skin lesions?". Two independent reviewers selected the final sample using inclusion/exclusion criteria using the EndNote® and Rayyan programs. Data was extracted using an adapted form and reported using the PRISMA checklist extension, and the protocol was registered in the Open Science Framework (OSF). RESULTS: 21 articles were selected, with nanofibers, nanogels and nanomembranes as the nanocomposites described in wound healing, alone or in association with other therapies: negative pressure and elastic. Silver nanomaterials stand out in accelerating healing due to their antimicrobial and anti-inflammatory action, but caution should be exercised due to the risk of cytotoxicity and microbial resistance. CONCLUSION: Nanocomposites used in wound treatment are effective in accelerating healing and reducing costs, and the addition of bioactives to nanomaterials has added extra properties that contribute to healing.

Multifunctional in vitro, in silico and DFT analyses on antimicrobial BagremycinA biosynthesized by Micromonospora chokoriensis CR3 from Hieracium canadense.

Among the actinomycetes in the rare genera, Micromonospora is of great interest since it has been shown to produce novel therapeutic compounds. Particular emphasis is now on its isolation from plants since its population from soil has been extensively explored. The strain CR3 was isolated as an endophyte from the roots of Hieracium canadense, and it was identified as Micromonospora chokoriensis through 16S gene sequencing and phylogenetic analysis. The in-vitro analysis of its extract revealed it to be active against the clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Candida tropicalis (15 mm). No bioactivity was observed against Gram-negative bacteria, Escherichia coli ATCC 25922, and Klebsiella pneumoniae ATCC 706003. The Micromonospora chokoriensis CR3 extract was also analyzed through the HPLC-DAD-UV-VIS resident database, and it gave a maximum match factor of 997.334 with the specialized metabolite BagremycinA (BagA). The in-silico analysis indicated that BagA strongly interacted with the active site residues of the sterol 14-α demethylase and thymidylate kinase enzymes, with the lowest binding energies of - 9.7 and - 8.3 kcal/mol, respectively. Furthermore, the normal mode analysis indicated that the interaction between these proteins and BagA was stable. The DFT quantum chemical properties depicted BagA to be reasonably reactive with a HOMO-LUMO gap of (ΔE) of 4.390 eV. BagA also passed the drug-likeness test with a synthetic accessibility score of 2.06, whereas Protox-II classified it as a class V toxicity compound with high LD50 of 2644 mg/kg. The current study reports an endophytic actinomycete, M. chokoriensis, associated with H. canadense producing the bioactive metabolite BagA with promising antimicrobial activity, which can be further modified and developed into a safe antimicrobial drug.

Antimicrobial sesterterpenoids with a unique 5/8/6/5 tetracyclic carbon-ring-system and diepoxide polyketides from a deep sea-sediment-sourced fungus Chaetomium globosum SD-347.

Two new sesterterpenoids, sesterchaetins A and B (1 and 2), and two new diepoxide polyketides, chaetoketoics A and B (3 and 4), were characterized from the culture extract of Chaetomium globosum SD-347, a fungal strain derived from deep sea-sediment. Their structures and absolute configurations were unambiguously determined by detailed NMR, mass spectra, and X-ray crystallographic analysis. Compounds 1 and 2 contained a distinctive 5/8/6/5 tetracyclic carbon-ring-system, which represented a rarely occurring natural product framework. The new isolates 1-4 exhibited selective antimicrobial activities against human and aquatic pathogenic bacteria and plant-pathogenic fungi.

Targeting the cysteine biosynthesis pathway in microorganisms: Mechanism, structure, and drug discovery.

Owing to the global health crisis of resistant pathogenic infections, researchers are emphasizing the importance of novel prevention and control strategies. Existing antimicrobial drugs predominantly target a few pathways, and their widespread use has pervasively increased drug resistance. Therefore, it is imperative to develop new antimicrobial drugs with novel targets and chemical structures. The de novo cysteine biosynthesis pathway, one of the microbial metabolic pathways, plays a crucial role in pathogenicity and drug resistance. This pathway notably differs from that in humans, thereby representing an unexplored target for developing antimicrobial drugs. Herein, we have presented an overview of cysteine biosynthesis pathways and their roles in the pathogenicity of various microorganisms. Additionally, we have investigated the structure and function of enzymes involved in these pathways as well as have discussed drug design strategies and structure-activity relationships of the enzyme inhibitors. This review provides valuable insights for developing novel antimicrobials and offers new avenues to combat drug resistance.

Pradimicin U, a promising antimicrobial agent isolated from a newly found Nonomuraea composti sp. nov.

Pradimicin U is a new dihydrobenzo[a]naphthacenequinone compound found to be active on a screen designed to investigate compounds with antimicrobial activity, produced by the actinomycete designated strain FMUSA5-5T. The strain was isolated from a bio-fertilizer of Musa spp. collected from Suphanburi province, Thailand. The chemotaxonomic characteristics and 16S rRNA gene analysis revealed that strain FMUSA5-5T is a member of the genus Nonomuraea. Low genome-based taxonomic criteria, average nucleotide identity (ANI) (82.8-88.3%), average amino-acid identity (AAI) (79.4-87.3%), and digital DNA-DNA hybridization (dDDH) (29.5-38.5%) values and several phenotypic differences between strain FMUSA5-5T and its closest type strains of the genus Nonomuraea indicated that strain FMUSA5-5T represents a novel species of the genus Nonomuraea and the name Nonomuraea composti sp. nov. is proposed for the strain. The crude extract from the culture broth of strain FMUSA5-5T displayed promising antimicrobial activity against several pathogens and led to the isolation of a novel secondary metabolite, pradimicin U. Interestingly, this compound displayed a broad spectrum of biological activities such as antimalarial activity against Plasmodium falciparum K1 (IC50 value = 3.65 µg/mL), anti-Mycobacterium tuberculosis H37Ra (MIC value = 25.0 µg/mL), anti-Alternaria brassicicola BCC 42724 (MIC value = 25.0 µg/mL), anti-Bacillus cereus ATCC 11778 and anti-Staphylococcus aureus ATCC 29213 (MIC values = 6.25 and 1.56 µg/mL, respectively). Moreover, the compound possessed strong anti-human small cell lung cancer (NCI-H187) activity with IC50 value of 5.69 µg/mL, while cytotoxicity against human breast cancer (MCF-7) and Vero cells was very weak (IC50 values of 52.49 and 21.84 µg/mL, respectively).

Hydroxypropyl chitosan/ε-poly-l-lysine based injectable and self-healing hydrogels with antimicrobial and hemostatic activity for wound repair.

The biggest obstacle to treating wound healing continues to be the production of simple, inexpensive wound dressings that satisfy the demands associated with full process of repair at the same time. Herein, a series of injectable composite hydrogels were successfully prepared by a one-pot method by utilizing the Schiff base reaction as well as hydrogen bonding forces between hydroxypropyl chitosan (HCS), ε-poly-l-lysine (EPL), and 2,3,4-trihydroxybenzaldehyde (TBA), and multiple cross-links formed by the reversible coordination between iron (III) and pyrogallol moieties. Notably, hydrogel exhibits excellent physicochemical properties, including injectability, self-healing, water retention, and adhesion, which enable to fill irregular wounds for a long period, providing a suitable moist environment for wound healing. Interestingly, the excellent hemostatic properties of the hydrogel can quickly stop bleeding and avoid the serious sequelae of massive blood loss in acute trauma. Moreover, the powerful antimicrobial and antioxidant properties also protect against bacterial infections and reduce inflammation at the wound site, thus promoting healing at all stages of the wound. The study of biohydrogel with multifunctional integration of wound treatment and smart medical treatment is clarified by this line of research.

The quantitative molecular weight-antimicrobial activity relationship for chitosan polymers, oligomers, and derivatives.

Chitosan and chitosan derivatives can kill pathogenic microorganisms including bacteria and fungi. The antimicrobial activity is dependent on the degree of acetylation, substituent structure, and molecular weight. Over the past four decades, numerous studies have endeavored to elucidate the relationship between molecular weight and the activity against microorganisms. However, investigators have reported divergent and, at times, conflicting conclusions. Here a bilinear equation is proposed, delineating the relationship between antimicrobial activity, defined as log (1/MIC), and the molecular weight of chitosan and chitosan derivatives. Three constants AMin, AMax, and CMW govern the shape of the curve determined by the equation. The constant AMin denotes the minimal activity expected as the molecular weight tends towards zero while AMax represents the maximal activity observed for molecular weights exceeding CMW, the critical molecular weight required for max activity. This equation was applied to analyze data from seven studies conducted between 1984 and 2019, which reported MIC (Minimum Inhibitory Concentration) values against bacteria and fungi for various molecular weights of chitosan and its derivatives. All the 29 datasets exhibited a good fit (R2 ≥ 0.5) and half excellent (R2 ≥ 0.95) fit to the equation. The CMW generally ranged from 4 to 10 KD for datasets with an excellent fit to the equation.

Quantitative and qualitative evaluation of antimicrobial usage: the first step for antimicrobial stewardship.

The identification of antimicrobial use patterns is essential for determining key targets for antimicrobial stewardship interventions and evaluating the effectiveness thereof. Accurately identifying antimicrobial use patterns requires quantitative evaluation, which focuses on measuring the quantity and frequency of antimicrobial use, and qualitative evaluation, which assesses the appropriateness, effectiveness, and potential side effects of antimicrobial prescriptions. This paper summarizes the quantitative and qualitative methods used to evaluate antimicrobials, drawing insights from overseas and domestic cases.

Evaluation of antimicrobial and non-steroidal anti-inflammatory treatments for BRD on health and welfare in fattening bulls: a cross-sectional study.

Our study aimed to evaluate the effect of different treatments for BRD on health and welfare in fattening bulls. A total of 264 bulls were enrolled. Welfare was assessed on day 2 (T0) and day 15 (T1) after arrival. A decrease in the welfare level was observed from T0 to T1. All bulls were inspected clinically at T0 and T1 revealing an increase of skin lesions and lameness in T1. In both periods, a high incidence of respiratory disease was observed. A prevalence of 79.55% and 95.45% of Mycoplasma bovis using RT-PCR and culture at T0 and T1 respectively was observed. Blood samples were collected for haematology at T0 and T1. At T0, 36 animals were individually treated for BRD with an antimicrobial (IT), 54 received a metaphylactic treatment with tulathromycin (M), 150 received a metaphylactic treatment with tulathromycin plus a second antimicrobial (M + IT) whereas 24 were considered healthy and therefore not treated (NT). Additionally, 128 were treated with a non-steroid anti-inflammatory (NSAID). Neutrophils of M + IT were significantly higher than groups NT and M and the lymphocytes of M + IT were significantly lower than that of IT. White blood cells, neutrophils and N/L ratio of animals treated with an NSAID was significantly higher than that not treated. Lung inspection of 172 bulls at the abattoir indicated that 92.43% presented at least one lung lesion. A statistically significant effect of the NSAID treatment on the lung lesions was observed. Our findings indicate that BRD was a major welfare and health concern and evidence the difficulties of antimicrobial treatment of M. bovis.

Fabrication and characterization of a new eco-friendly sulfonamide-chitosan derivative with enhanced antimicrobial and selective cytotoxicity properties.

Chitosan (CH) exhibits low antimicrobial activity. This study addresses this issue by modifying the chitosan with a sulfonamide derivative, 3-(4-(N,N-dimethylsulfonyl)phenyl)acrylic acid. The structure of the sulfonamide-chitosan derivative (DMS-CH) was confirmed using Fourier transform infrared spectroscopy and Nuclear magnetic resonance. The results of scanning electron microscopy, thermal gravimetric analysis, and X-ray diffraction indicated that the morphology changed to a porous nature, the thermal stability decreased, and the crystallinity increased in the DMS-CH derivative compared to chitosan, respectively. The degree of substitution was calculated from the elemental analysis data and was found to be moderate (42%). The modified chitosan exhibited enhanced antimicrobial properties at low concentrations, with a minimum inhibitory concentration (MIC) of 50 µg/mL observed for B. subtilis and P. aeruginosa, and a value of 25 µg/mL for S. aureus, E. coli, and C. albicans. In the case of native chitosan, the MIC values doubled or more, with 50 µg/mL recorded for E. coli and C. albicans and 100 µg/mL recorded for B. subtilis, S. aureus, and P. aeruginosa. Furthermore, toxicological examinations conducted on MCF-7 (breast adenocarcinoma) cell lines demonstrated that DMS-CH exhibited greater toxicity (IC50 = 225.47 µg/mL) than pure CH, while still maintaining significant safety limits against normal lung fibroblasts (WI-38). Collectively, these results suggest the potential use of the newly modified chitosan in biomedical applications.

Cryo-storage of porcine hides at the industrial scale for tissue engineering and regenerative medicine application.

BACKGROUND: The industrial scale cryo-storage of raw tissue materials requires a robust, low-cost and easy-to-operate method that can facilitate the down-stream process. OBJECTIVE: The study was aimed to develop the multifunctional protective solutions (MPS) for transportation at ambient conditions and also subsequent cryo-storage below -20 degree C of raw porcine hides for tissue engineering and regenerative medicine. MATERIALS AND METHODS: Protective solutions with antimicrobial activity and proteinase-inhibiting activity were developed and tested for its efficacy in preserving the extracellular matrix of porcine dermis from microbial spoilage, proteolytic degradation, freeze damage and excessive dehydration during shipping and cryo-storage. The MPSs contained phosphate-buffered saline with ethylene diamine tetra acetic acid (EDTA) added as chelator and proteinase inhibitor, as well as glycerol or maltodextrin (M180) as cryoprotectants. RESULTS: MPSs prepared with EDTA and glycerol or M180 had significant antimicrobial activity and proteinase-inhibiting activity during the period of shipping and handling. Glycerol and M180 prevented eutectic salt precipitation and excessive freeze dehydration upon cryo-storage of porcine hides. Without glycerol or M180, hides could be freeze-dehydrated to the low hydration at ~0.4 g/g dw, and formed irreversible plications after freezing. A critical hydration (0.8~0.9 g/g dw) was observed for the extracellular matrix of porcine dermis, and dehydration to a lower level could impose enormous stress and potential damage. The soaking of porcine hides in MPSs decreased water content as glycerol and M180 entered into dermis. Upon equilibration, the glycerol content in the tissue was about 94% of the incubating glycerol solution, but the M180 content in the tissue was only about 50% of the incubating M180 solution, indicating that M180 did not get into the entire aqueous domain within dermis. MPSs reduced ice formation and increased the unfrozen water content of porcine raw hides upon cryo-storage. CONCLUSION: MPSs prepared with EDTA and glycerol or M180 have antimicrobial activity and proteinase-inhibiting activity, which can be used for transportation and cryo-storage of raw hides at the industrial scale. Glycerol at 7.5% w/v and M180 at 20% w/v were sufficient to prevent freeze damage and excessive freeze dehydration. Doi.org/10.54680/fr24310110312.

Hindering the biofilm of microbial pathogens and cancer cell lines development using silver nanoparticles synthesized by epidermal mucus proteins from Clarias gariepinus.

Scientists know very little about the mechanisms underlying fish skin mucus, despite the fact that it is a component of the immune system. Fish skin mucus is an important component of defence against invasive infections. Recently, Fish skin and its mucus are gaining interest among immunologists. Characterization was done on the obtained silver nanoparticles Ag combined with Clarias gariepinus catfish epidermal mucus proteins (EMP-Ag-NPs) through UV-vis, FTIR, XRD, TEM, and SEM. Ag-NPs ranged in size from 4 to 20 nm, spherical in form and the angles were 38.10°, 44.20°, 64.40°, and 77.20°, Where wavelength change after formation of EMP-Ag-NPs as indicate of dark brown, the broad band recorded at wavelength at 391 nm. Additionally, the antimicrobial, antibiofilm and anticancer activities of EMP-Ag-NPs was assessed. The present results demonstrate high activity against unicellular fungi C. albicans, followed by E. faecalis. Antibiofilm results showed strong activity against both S. aureus and P. aeruginosa pathogens in a dose-dependent manner, without affecting planktonic cell growth. Also, cytotoxicity effect was investigated against normal cells (Vero), breast cancer cells (Mcf7) and hepatic carcinoma (HepG2) cell lines at concentrations (200-6.25 µg/mL) and current results showed highly anticancer effect of Ag-NPs at concentrations 100, 5 and 25 µg/mL exhibited rounding, shrinkage, deformation and granulation of Mcf7 and HepG2 with IC50 19.34 and 31.16 µg/mL respectively while Vero cells appeared rounded at concentration 50 µg/mL and normal shape at concentration 25, 12.5 and 6.25 µg/ml with IC50 35.85 µg/mL. This study evidence the potential efficacy of biologically generated Ag-NPs as a substitute medicinal agent against harmful microorganisms. Furthermore, it highlights their inhibitory effect on cancer cell lines.

How Should We Manage Antimicrobial Resistance in Resource-Limited Settings?

Patients living in low- and middle-income countries (LMICs) shoulder the greatest burden of infections caused by antimicrobial-resistant pathogens. Speedy access to appropriate broad-spectrum antimicrobials significantly improves health outcomes and reduces transmission of antimicrobial-resistant pathogens, but persons living in LMICs have compromised access to these antimicrobials. This article considers how inequities in microbiology diagnostics, antimicrobial access, and antimicrobial affordability influence outcomes for patients infected with antimicrobial-resistant pathogens who live in resource-limited settings.

Integrative Genomics and Bioactivity-Guided Isolation of Novel Antimicrobial Compounds from Streptomyces sp. KN37 in Agricultural Applications.

Actinomycetes have long been recognized as an important source of antibacterial natural products. In recent years, actinomycetes in extreme environments have become one of the main research directions. Streptomyces sp. KN37 was isolated from the cold region of Kanas in Xinjiang. It demonstrated potent antimicrobial activity, but the primary active compounds remained unclear. Therefore, we aimed to combine genomics with traditional isolation methods to obtain bioactive compounds from the strain KN37. Whole-genome sequencing and KEGG enrichment analysis indicated that KN37 possesses the potential for synthesizing secondary metabolites, and 41 biosynthetic gene clusters were predicted, some of which showed high similarity to known gene clusters responsible for the biosynthesis of antimicrobial antibiotics. The traditional isolation methods and activity-guided fractionation were employed to isolate and purify seven compounds with strong bioactivity from the fermentation broth of the strain KN37. These compounds were identified as 4-(Diethylamino)salicylaldehyde (1), 4-Nitrosodiphenylamine (2), N-(2,4-Dimethylphenyl)formamide (3), 4-Nitrocatechol (4), Methylsuccinic acid (5), Phenyllactic acid (6) and 5,6-Dimethylbenzimidazole (7). Moreover, 4-(Diethylamino)salicylaldehyde exhibited the most potent inhibitory effect against Rhizoctonia solani, with an EC50 value of 14.487 mg/L, while 4-Nitrosodiphenylamine showed great antibacterial activity against Erwinia amylovora, with an EC50 value of 5.715 mg/L. This study successfully isolated several highly active antimicrobial compounds from the metabolites of the strain KN37, which could contribute as scaffolds for subsequent chemical synthesis. On the other hand, the newly predicted antibiotic-like substances have not yet been isolated, but they still hold significant research value. They are instructive in the study of active natural product biosynthetic pathways, activation of silent gene clusters, and engineering bacteria construction.

Enhancing Mechanical and Antimicrobial Properties of Dialdehyde Cellulose-Silver Nanoparticle Composites through Ammoniated Nanocellulose Modification.

Given the widespread prevalence of viruses, there is an escalating demand for antimicrobial composites. Although the composite of dialdehyde cellulose and silver nanoparticles (DAC@Ag1) exhibits excellent antibacterial properties, its weak mechanical characteristics hinder its practical applicability. To address this limitation, cellulose nanofibers (CNFs) were initially ammoniated to yield N-CNF, which was subsequently incorporated into DAC@Ag1 as an enhancer, forming DAC@Ag1/N-CNF. We systematically investigated the optimal amount of N-CNF and characterized the DAC@Ag1/N-CNF using FT-IR, XPS, and XRD analyses to evaluate its additional properties. Notably, the optimal mass ratio of N-CNF to DAC@Ag1 was found to be 5:5, resulting in a substantial enhancement in mechanical properties, with a 139.8% increase in tensile elongation and a 33.1% increase in strength, reaching 10% and 125.24 MPa, respectively, compared to DAC@Ag1 alone. Furthermore, the inhibition zones against Escherichia coli and Staphylococcus aureus were significantly expanded to 7.9 mm and 15.9 mm, respectively, surpassing those of DAC@Ag1 alone by 154.8% and 467.9%, indicating remarkable improvements in antimicrobial efficacy. Mechanism analysis highlighted synergistic effects from chemical covalent bonding and hydrogen bonding in the DAC@Ag1/N-CNF, enhancing the mechanical and antimicrobial properties significantly. The addition of N-CNF markedly augmented the properties of the composite film, thereby facilitating its broader application in the antimicrobial field.