Molekulyarnaya Biologiya最新文献

{"title":"[Antibiotic Resistance Genes in Cattle Gut Microbiota: Influence of Housing Conditions].","authors":"Sh A Begmatov, A V Beletsky, A L Rakitin, A P Lukina, L O Sokolyanskaya, A V Rakitin, L B Glukhova, A V Mardanov, O V Karnachuk, N V Ravin","doi":"10.31857/S0026898424060105, EDN: IALWAS","DOIUrl":"10.31857/S0026898424060105, EDN: IALWAS","url":null,"abstract":"<p><p>Resistance to antimicrobial drugs is an urgent problem not only in public health, but also in animal husbandry. The widespread use of antimicrobials in feed additives is one of the main reasons for the rapid spread of antibiotic resistance in the microbiota of the gastrointestinal tract of farm animals. To characterize antibiotic resistance genes (resistome), we performed metagenomic analysis of the feces of 24 cattle from different regions of Russia, including cows of different breeds and yaks. Animals differed in the type of housing: year-round on pastures or in barns of conventional farms, with consumption of feed additives. Although genes of resistance to aminoglycosides, β-lactams, glycopeptides, MLS antibiotics (macrolides, lincosamides, and streptogramins), phenicols, and tetracyclines were detected in samples from both groups of animals, the content of the resistome in the fecal microbiome of stall-bred cattle was about ten times higher than in animals kept on pastures. The resistome of stall cattle was dominated by β-lactamases and tetracycline resistance genes, the content of which in the microbiome was 24 and 60 times higher, respectively, than in animals kept on pastures. Apparently, the spread of resistance to β-lactams and tetracyclines in stall cattle reflects the active use of these antibiotics in livestock production. Metagenomic analysis of livestock feces can be used to quantify antibiotic resistance genes for the purpose of monitoring antimicrobial drugs used in animal husbandry.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 6","pages":"996-1006"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Distribution of Antibiotic Resistance Genes in Microbial Communities: The Impact of Anthropogenic Pollution].","authors":"I S Sazykin, M A Sazykina, A R Litsevich","doi":"10.31857/S0026898424060056, EDN: HMZHOY","DOIUrl":"10.31857/S0026898424060056, EDN: HMZHOY","url":null,"abstract":"<p><p>Issues related to the spread of antibiotic resistance genes in environmental microbial communities are considered. \"Hotspots\" of adaptive evolution, accumulation, and spread of antibiotic-resistant bacteria and genetic material of antibiotic resistance are highlighted. Such \"hotspots\" include anthropogenic ecosystems, such as municipal wastewater treatment plants, municipal solid waste landfills, livestock enterprises, and agrocenoses. The influence of various types of pollutants and biotic factors on enhancement of mutagenesis and horizontal transfer of antibiotic resistance genes is considered. The role of mobile genetic elements in mobilization and accelerated spread of resistance determinants is shown. Special attention is paid to the role of oxidative stress and stress regulons, which are activated for realization and control of molecular genetic mechanisms of adaptive evolution of bacteria and the horizontal distribution of genetic material in bacterial populations. Oxidative stress is identified as one of the main activators of genome destabilization and adaptive evolution of bacteria.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 6","pages":"937-952"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[History of the Creation of a New Generation of Antibiotics of the Group of Polycyclic Glycopeptides].","authors":"E N Olsufyeva","doi":"10.31857/S0026898424060029, EDN: HNBCOO","DOIUrl":"10.31857/S0026898424060029, EDN: HNBCOO","url":null,"abstract":"<p><p>Increased resistance to polycyclic glycopeptide antibiotics has become a serious problem for chemotherapy of infections caused by resistant Gram-positive bacteria. Chemical modification of known natural antibiotics is the main direction in the creation of the next generation of anti-infective drugs. Over the past two decades, a series of hydrophobic glycopeptide analogues active against resistant strains of Gram-positive bacteria have been developed, three of which - oritavancin, telavancin, and dalbavancin - were approved by the US Food and Drug Administration (FDA) in 2013-2014 for the treatment of infections caused by sensitive and resistant strains of staphylococci and enterococci. It has been established that hydrophobic derivatives of glycopeptides can act on resistant strains of bacteria by a mechanism that does not allow binding to the modified target of resistant bacteria. Understanding the mechanism of action of natural and modified glycopeptides is considered as the basis for the rational design of compounds with valuable properties to achieve fundamental results. The possibility of using semi-synthetic glycopeptide analogues in the fight against viral infections caused by enveloped viruses is also considered. This review outlines the main ways of chemical design in creating a new generation of glycopeptide antibiotics that overcome resistance to Gram-positive pathogens and the mechanisms of their action.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 6","pages":"862-886"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Toxicity Study of the Pharmacological Pair of Encapsulated Citrobacter freundii C115H Methionine γ-Lyase/Methiin].","authors":"S V Revtovich, V V Kulikova, V S Koval, A D Lyfenko, V A Kazakov, A S Chernov, G B Telegin, A S Zemskaya, N V Anufrieva, E A Morozova, P N Solyev","doi":"10.31857/S0026898424060064, EDN: HMWQWG","DOIUrl":"10.31857/S0026898424060064, EDN: HMWQWG","url":null,"abstract":"<p><p>Acute and subchronic toxicity of the pharmacological pair based on encapsulated Citrobacter freundii C115H methionine γ-lyase enzyme/prodrug (methiin) was studied in female ICR mice. The drug showed a weak/moderate dose-dependent hepatotoxic effect. Most of the changes in liver morphology identified were insignificant or mild deviations from the norm. Long-term use of a single therapeutic dose per mouse of 1.5 U C. freundii C115H methionine γ-lyase @ (PEG-P(Asp)70/PLL70)-PIC-some/2 mg methiin led to a slight decrease in the weight of animals without obvious signs of intoxication. A quarter of the animals in this group had no deviations from the norm in liver morphology. No nephrotoxic effect was found in any study group.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 6","pages":"953-965"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Adapting Mouse Genome Editing Technique from Scratch Using in utero Electroporation].","authors":"J V Popova, V D Bets, E S Omelina, L V Boldyreva, E N Kozhevnikova","doi":"10.31857/S0026898424060142, EDN: IAETMS","DOIUrl":"10.31857/S0026898424060142, EDN: IAETMS","url":null,"abstract":"<p><p>Mouse genome modification requires costly equipment and highly skilled personnel to manipulate zygotes. A number of zygote electroporation techniques were reported to be highly efficient in gene delivery. One of these methods called i-GONAD (improved Genome-editing via Oviductal Nucleic Acids Delivery) describes electroporation-based gene transfer to zygotes in utero. Here we adopted this technology to develop an easy-to-use and cost-effective pipeline enabling mouse genome-editing from scratch with minimal requirements to operator skills and animal use. We chose the CRISPR/Cas9 system as a genome editing tool and i-GONAD as a gene delivery method to produce Il10 knockout in C57BL/6 mice. Three animals out of 13 delivered pups (23%) were genetically compromised at Il10 locus suggesting the feasibility of the approach. This protocol provides detailed description of the used technical settings paired with troubleshooting tips and could be of interest to those who aim at establishing in-house mouse transgenesis pipeline at minimal equipment cost from scratch.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 6","pages":"1041-1051"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Enzymes of ADP-Heptose Biosynthesis As Targets for the Creation of Broad-Spectrum Antibacterial Drugs].","authors":"T A Seregina, I Yu Petrushanko, K V Lobanov, R S Shakulov, A S Mironov","doi":"10.31857/S0026898424060048, EDN: HMZWNA","DOIUrl":"10.31857/S0026898424060048, EDN: HMZWNA","url":null,"abstract":"<p><p>Solving the problem of multidrug resistance currently requires the development of nonstandard approaches, since the potential for creating new antibiotics is almost exhausted. Controlling the metabolism of a pathogen in order to increase its susceptibility to antibacterial therapy is considered the most promising area of research for the creation of new combination drugs. In recent years, the number of studies devoted to investigation the role of the biosynthesis of the cell wall component ADP-heptose in the sensitivity of bacteria to antibiotics, as well as in the pathogenesis of bacterial infection, has increased. This review examines the main directions of scientific research in the field of use of ADP-heptose and its analogues in the treatment of bacterial infections. The exclusive role of ADP-heptose in the induction of an immune response is known through the activation of the NF-κB signaling pathway and the synthesis of pro-inflammatory cytokines. Our latest work has shown that disruption of the synthesis of ADP-heptose and the efflux of sedoheptulose-7-phosphate from the pentose phosphate pathway induces a redox imbalance and completely disorganizes the metabolism of low molecular weight thiols such as hydrogen sulfide, cysteine, and glutathione, which makes the bacterial cell extremely vulnerable to the action of antibiotics. We demonstrate that the hypersensitivity of ADP-heptose mutants to a wide range of antibiotics is explained by a new metabolic status rather than by changes in cell wall permeability. Thus, potential inhibitors of ADP-heptose biosynthesis can combine several positive qualities: an immunomodulatory effect and a powerful potentiating effect in combination with antibiotic therapy.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 6","pages":"927-936"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Expression Profiles of TRIM Family Genes in Neuronal and Glial Cell Cultures of Healthy Donors and Patients with Parkinson's Disease under Normal Conditions and Upon Neuroinflammation].","authors":"V V Nenasheva, E V Novosadova, T P Gerasimova, L V Novosadova, A Y Kotok, E L Arsenieva, E A Stepanenko, I A Grivennikov, V Z Tarantul","doi":"10.31857/S0026898424060172, EDN: HZSRSN","DOIUrl":"10.31857/S0026898424060172, EDN: HZSRSN","url":null,"abstract":"<p><p>Proteins of the TRIM family are involved in both innate immunity and the nervous system processes and may play an important role in the development of neurodegenerative diseases. In this work, we analyzed the expression of 35 genes of the TRIM family in neural progenitors (NPs), terminally differentiated neurons (TDNs) and glial derivatives (NGs) obtained from induced pluripotent stem cells (iPSCs) of healthy donors (HD) and patients with Parkinson's disease (PD), in the absence of inflammatory stimuli and upon the induction of a nonspecific inflammatory response under the influence of TNFα. In NPs and TDNs of PD patients, compared with HD cells, differences in expression were observed for only a small number of TRIM genes. Under the influence of TNFα in TDNs, the expression of individual TRIM genes was activated, which was more significant in the cells of patients with PD compared to cells of HDs. In NGs of PD patients, the expression of many TRIM genes was initially reduced compared to HD cells and remained low or further decreased after exposure to TNFα. The data obtained demonstrate differences in the network of the TRIM family members in PD neurons and glia compared to control, and also show the multidirectional influence of the inflammatory stimulus on the expression of a number of TRIM genes in these types of cells. Considering the important role of many TRIM genes in the functioning of the innate immune system, it can be assumed that, in PD, more significant disturbances in the functioning of genes of this family occur in glia compared to neurons.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 6","pages":"1075-1086"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[New Epigenetic Markers of Age-Dependent Changes in the Cardiovascular System].","authors":"L M Ermakova, E A Davydova, E V Kondakova, K V Kuchin, M V Vedunova","doi":"10.31857/S0026898424060161, EDN: HZSYRB","DOIUrl":"10.31857/S0026898424060161, EDN: HZSYRB","url":null,"abstract":"<p><p>Cardiovascular diseases remain a predominant global cause of mortality, with a noteworthy rise in the risk of morbidity with advancing age. Besides, it accompanied by a phenomenon of disease rejuvenation in the circulatory system. Currently, epigenetic modifications play a key role in the genesis of cardiovascular diseases (CVD), influencing the complex interaction between genotype and phenotype variability. Consequently, delving into the realm of epigenetic markers offers a promising avenue to unravel the molecular underpinnings of cardiovascular disease pathogenesis. This study endeavors to pinpoint epigenetic markers intricately linked with age-related transformations in the cardiovascular system. The study revealed a robust correlation with age for two cardiological parameters: R wave tension in the augmented left arm lead (RaVL) and carotid-femoral pulse wave velocity (cfPWV). Moreover, these parameters exhibited a strong correlation with the DNA methylation level of 21 CpG-sites (CpGs) examined through the Illumina EPIC array. Notably, the majority of these identified CpG-sites are affiliated with genes involved in the development of pathologies of the cardiovascular system.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 6","pages":"1061-1074"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Synthesis and Antimicrobial Activity of Thiosulfinates and Allicin Analogues].","authors":"V M Puchkov, A D Lyfenko, V S Koval, S V Revtovich, V V Kulikova, N V Anufrieva, A S Zemskaya, E A Morozova, P N Solyev","doi":"10.31857/S0026898424060074, EDN: HMWIWS","DOIUrl":"10.31857/S0026898424060074, EDN: HMWIWS","url":null,"abstract":"<p><p>Diallyl thiosulfinate (allicin) effectively inhibits the growth of various microorganisms, including antibiotic-resistant strains, so it can be considered to be a broad-spectrum antimicrobial compound. However, its instability in the bloodstream hinders its use as a therapeutic agent. We have synthesized a number of allicin analogues, both natural and synthetic, and evaluated in vitro their antimicrobial properties against Staphylococcus aureus and Candida albicans. The synthesized compounds were shown to exhibited more pronounced antifungal activity than antibacterial. Among the compounds obtained, synthetic di-(2,2,2-trichloroethyl) ester of 3,3'-[(thio)sulfinyl]dipropionic acid effectively inhibited the growth of both fungi and bacteria at concentrations comparable to those of known antimicrobial agents used in medical practice.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 6","pages":"966-974"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Surface-Enhanced Raman Scattering to Improve the Sensitivity of the MTT Assay].","authors":"V A Mushenkov, D A Lukyanov, N F Meshcheryakova, V I Kukushkin, E G Zavyalova","doi":"10.31857/S0026898424060134, EDN: IAFGAM","DOIUrl":"10.31857/S0026898424060134, EDN: IAFGAM","url":null,"abstract":"<p><p>Currently, empirical therapy regimens are often used in the treatment of infectious diseases that are not based on data on pathogen resistance. One of the main reasons for the unjustified prescription of antibacterial drugs is the lack of rapid and at the same time universal methods of determining the antibiotic resistance of the pathogen. The most widely used culture techniques, such as the microdilution method, require a long time to generate the necessary number of bacterial cells. Less time-consuming methods of resistance assessment (genomic or proteomic) are based on the determination of specific markers (resistance genes, overexpression of certain proteins, etc.); in this case, the specific protocol is most often applicable to a narrow number of both microorganism strains and antibiotics. Previously, we demonstrated the possibility of using Raman spectroscopy (RS) technology for quantitative determination of the product of bacterial cell activity in the MTT assay, formazan, directly in the cell suspension. The absence of the formazan isolation step simplifies the assay and increases its accuracy. The analysis time did not exceed 2 h while maintaining the versatility of the MTT assay itself. Limitations of the developed protocol for RS detection of the MTT assay results include a high sensitivity threshold of 10^(7) CFU/mL for the bacterial cell concentration, so a preliminary stage of cultivation is necessary for samples with a low bacterial content. Here, we propose a method to increase the sensitivity of formazan determination by utilizing the effect of surface-enhanced Raman scattering (SERS) on gold nanoparticles. As a result of this study, the optimal conditions for SERS analysis of formazan in both solution and suspension of Escherichia coli cells are selected. Formazan signal amplification due to the use of SERS on gold nanoparticles instead of RS allowed us to reduce the sensitivity threshold for the number of bacterial cells in the sample by at least 30 times, up to 3 x 10^(5) CFU/mL. This sensitivity is not the limit of the SERS technology capabilities because the introduction of other types of nanoparticles (more optimal in shape, size, concentration, etc.) into the experiment will allow one to achieve even higher signal amplification.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"58 6","pages":"1031-1040"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}