While studying the prevalence and profile of antibiotic resistance among E. coli isolated from the feces of calves with signs of colibacillosis, a strain with a wide spectrum of drug resistance was isolated. Whole-genome sequencing, followed by bioinformatic processing and the annotation of genes of this strain, showed that the genome has a total length of 4,803,482 bp and contains 4986 genes, including 122 RNA genes. A total of 31% of the genes are functionally significant and represent 26 functional groups. Additionally, 55 antibiotic resistance genes were revealed. A phenotypic drug-resistance study was performed according to CASFM and CLSI guidelines, which showed that the investigated strain was resistant to eight antibacterial drugs of different classes, including colistin. This is the first report on the AMR profile of an E. coli isolate obtained from a sick calf with evidence of escherichiosis in Kazakhstan. The provided information on the genome will be valuable in studying the evolution and development of antibiotic-resistant forms of E. coli and increase our knowledge of pathogenicity. It may also be a source for future comparative studies of the virulence and drug resistance of E. coli isolates.

Organic acids, as natural metabolites, play crucial roles in human metabolism and health. Tumor Necrosis Factor (TNF), a pivotal mediator in immune regulation and inflammation, is a key therapeutic target. We evaluated ten organic acids as TNF modulators using in silico molecular docking, followed by detailed ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling and molecular dynamics (MD) simulations for three lead candidates: gallic, aconitic, and crocetin acids. Their effects on TNF gene expression were then assessed in vivo using a mouse leukocyte model. The in silico results indicated that crocetin had the highest TNF binding affinity (−5.6 to −4.6 kcal/mol), while gallic acid formed the most stable protein-ligand complex during MD simulations, and aconitic acid established hydrogen bond interactions. ADMET analysis suggested potential pharmacokinetic limitations, including low permeability. Contrasting its high predicted binding affinity, in vivo gene expression analysis revealed that crocetin stimulated TNF synthesis, whereas gallic and aconitic acids acted as inhibitors. This research explores organic acids as potential TNF modulators, highlighting their complex interactions and providing a foundation for developing these compounds as anti-inflammatory agents targeting TNF-mediated diseases.

The spread of antibiotic-resistant pathogenic Escherichia coli poses a serious threat to calf health on livestock farms. With the decline in antibiotic therapy effectiveness, alternative approaches such as phage therapy are urgently needed. This study aimed to isolate lytic E. coli bacteriophages, characterize their properties, and evaluate the synergistic effects of their combined use with veterinary antibiotics against colibacillosis pathogens in calves. As a result of the work, 4 bacteriophages were isolated from wastewater from various cities of Kazakhstan: vB_EcoS_ABO/4, vB_EcoM_PL/4, vB_Eco_CWW/26, vB_EcoM_ShWW/46. Morphological, biological, and genomic analyses showed that the phages belong to different genera of the Caudoviricetes class, possess high lytic activity, broad host range, environmental stability, and lack genes associated with lysogeny, antibiotic resistance, or virulence. Interaction studies with antibiotics revealed synergistic or additive effects in over 75% of cases. These findings highlight the strong potential of the isolated bacteriophages for independent or adjunctive use in the treatment and prevention of colibacillosis in calves. However, further in vivo studies are required to definitively confirm their therapeutic efficacy.

One of the significant challenges of modern public health is the global spread of drug resistance among bacterial pathogens. According to WHO forecasts mortality from resistant bacterial infections by 2050 may reach up to 10 million cases per year. One of the ways to solve this problem is the mass introduction of phage therapy into medical practice, which requires the search, isolation, and study of lytic bacteriophages that can effectively fight resistant bacterial infections. In this study, we report on the genome of the lytic vB_EcoM_AMO3598 bacteriophage isolated from wastewater in Almaty city, targeting clinical, antibiotic-resistant E. coli strains. Bacteriophage vB_EcoM_AMO3598 possesses a double-stranded linear DNA genome of 145,425 bp in length containing 290 putative genes encoding proteins, including tRNA, and is a representative of the subfamily of Stephanstirmvirinae, genus Justusliebigvirus. The structure of the viral particles of phage vB_EcoM_AMO3598 has a myo-like shape with an icosahedral head and a contractile tail. The vB_EcoM_AMO3598 bacteriophage is known to be capable of lysing at least 4 clinical antibiotic-resistant E. coli strains. Up to 90% of viral particles are adsorbed within the first 4 minutes of phage infection. The latent period is 20 minutes, and the burst size is 218±28 phage particles per cell.

Roseofungin, a polyene macrolide antibiotic produced by Streptomyces roseoflavus, was evaluated for antiviral activity against Influenza A virus using complementary in vitro, in ovo, and preliminary in vivo toxicity models, supported by molecular docking and molecular dynamics simulations. The compound exhibited antiviral activity against multiple influenza A virus subtypes, including an oseltamivir-resistant H1N1 strain, with EC₅₀ values ranging from 2.0 to 2.5 μg/mL and selectivity indices of 20–25. Functional assays demonstrated that roseofungin interfered with early stages of the viral life cycle by reducing viral adsorption and partially inhibiting neuraminidase activity. In virucidal assays, treatment with roseofungin resulted in a 1.5–2.5 log₁₀ reduction in infectious viral titers. Acute toxicity studies in mice indicated low toxicity under the experimental conditions (LD₅₀ > 25 mg/kg). Molecular docking predicted favorable interactions of roseofungin with multiple influenza A virus proteins. Subsequent molecular dynamics simulations of the hemagglutinin–roseofungin complex maintained the stability of the predicted binding mode across three independent 50 ns simulations (150 ns cumulative). Collectively, these findings demonstrate that roseofungin possesses broad-spectrum antiviral activity against genetically diverse Influenza A virus strains and represents a promising lead compound for the development of novel membrane-active antiviral agents. Further studies are warranted to elucidate its molecular mechanism of action and to evaluate its therapeutic potential in vivo.

Anthocyanins are naturally occurring flavonoid pigments widely distributed in plants and are recognized for their antioxidant and anti-inflammatory activities. However, the molecular mechanisms underlying their potential immunomodulatory effects remain poorly characterized, particularly regarding their direct interactions with key signaling cytokines. In this study, a set of selected anthocyanins was investigated using a hierarchical computational workflow targeting three major pro-inflammatory cytokines: interleukin-2 (IL-2), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Molecular docking analyses identified primulin and antirrhinin as the most favorable binders, forming stabilizing hydrogen bonds and hydrophobic interactions within predicted cytokine interaction interfaces. To further assess the stability of these complexes, molecular dynamics simulations were performed under near-physiological conditions. Trajectory analyses demonstrated stable ligand–protein interactions and persistent intermolecular contacts throughout the 100 ns simulation period. These findings provide molecular-level insights into anthocyanin–cytokine interactions and highlight their potential relevance for modulating inflammatory signaling pathways.