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.

Staphylococcus aureus is a conditionally pathogenic microorganism and one of the main causative agents of antibiotic resistant nosocomial infections. In immunocompromised people, S. aureus infection can cause folliculitis, furuncles, impetigo, osteomyelitis, septic arthritis, sepsis, endocarditis, pneumonia and meningitis. In the presented work, sequencing of a methicillin-resistant S. aureus, strain 4233, was performed on the Illumina MiSeq platform, followed by bioinformatics processing and gene annotation using SPAdes, RAST and CARD programs and databases. The submitted genome is a total of 2,790,390 bp long and contains 2759 genes, including 82 RNA genes. 33 % of the genes are functionally significant and represent 25 functional groups. Fourteen genes encoding resistance factors to 14 different types of antibacterial drugs were predicted. The information provided on the genome of S. aureus, strain 4233 will be of value in investigating the evolution and formation of antibiotic-resistant forms of S. aureus.

The global burden of COVID-19 continues to rise, and despite significant progress in vaccine development, there remains a critical need for effective treatments for the severe inflammation and acute lung injury associated with SARS-CoV-2 infection. In this study, we explored the antiviral properties of a plant-derived complex consisting of flavonol and hydroxyorganic acid compounds. Our research focused on the ability of the flavonol and hydroxyorganic acid complex to suppress the activity of several key proteins involved in the replication and maturation of SARS-CoV-2. These proteins include ACE2 protein, HRV 3C Protease, and Mpro (Main Protease). It was shown that the plant-based complex effectively inhibited the activity of these viral proteins. In addition to its effects on viral proteins, the flavonol and hydroxyorganic acid complex were shown to suppress viral replication in Vero E6 cells. At a dose of 22 μg/mL, the drug demonstrated maximum antiviral activity, significantly reducing the replication of SARS-CoV-2 in vitro. In preliminary studies, the complex showed both prophylactic and therapeutic potential, suggesting that it may be useful for preventing infection, as well as reducing the severity of disease once an individual has been infected with SARS-CoV-2. Based on the compelling results of this study, we propose the flavonol and hydroxyorganic acid complex as a potential therapeutic compound for SARS-CoV-2. Its ability to inhibit key viral proteins, suppress viral replication and exhibit protective and therapeutic effects positions it as a valuable candidate for further research and clinical evaluation. As the global fight against SARS-CoV-2 continues, plant-based therapies like this complex could complement existing treatments and provide new options for managing and treating the disease.

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.

Аннотация Escherichia coli — комменсальный микроорганизм, способный приобретать определенные признаки вирулентности и вызывать широкий спектр заболеваний у домашних животных. На животноводческих фермах E. coli часто является причиной колибактериоза телят, что представляет собой серьезную проблему для их здоровья и благополучия, может привести к высокому уровню заболеваемости и смертности, и большим экономическим потерям. В частности, эта проблема может быть связана с неэффективностью лечения из-за наличия резистентности к противомикробным препаратам. Особенно это актуально для E. coli, которая обладает такими факторами вирулентности, как термостабильный токсин типа Ia (STa) и фимбрии K99. Недостаток информации об устойчивости к противомикробным препаратам у микрофлоры крупного рогатого скота в Казахстане побудил нас провести данное исследование, целью которого было оценить распространенность устойчивости к антибиотикам среди штаммов E. coli, выделенных из фекалий телят с клиническими признаками кишечной инфекции. В результате фенотипического тестирования чувствительности к антибиотикам полученных изолятов было выявлено, что общая распространенность антимикробной резистентности у изолятов E. coli была очень высокой для большинства из восьми протестированных классов противомикробных препаратов. Самый высокий уровень резистентности среди изолятов был обнаружен к аминогликозидам (87,3%), поликетидам (60%) и аминопенициллинам (57 %), за ними следовали сульфаниламиды (47%), амфениколы (43%) и фторхинолоны (33%). Самый низкий уровень резистентности наблюдался к колистину (3%).

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.