Biology subjects

Reva, O. N.

Publications and source records attributed to Reva, O. N..

4 recordsLinked to original sources

bioRxiv2026

Genetic and epigenetic diversity of Salmonella enterica isolates from Kazakhstan from clinical and veterinary sources

BackgroundSalmonella enterica is a major cause of foodborne and invasive infections worldwide. Increasing antimicrobial resistance and adaptation to diverse ecological niches require an improved understanding of the genetic and epigenetic diversity of circulating strains. This study investigated the genomic and epigenetic diversity of S. enterica isolates collected in Kazakhstan from clinical, animal, and environmental sources. MethodsWhole-genome sequencing was performed using the Illumina sequencing platform. Several selected strains were additionally sequenced using PacBio SMRT technology for DNA methylation profiling. Genome assembly, plasmid reconstruction, MLST genotyping, and analyses of virulence genes, antimicrobial resistance determinants, and genome methylation associated with restriction-modification (RM) systems and orphan methyltransferases were performed using established bioinformatics tools. ResultsThe ST11 genotype predominated among clinical isolates, but these strains formed distinct clusters differing in plasmid composition, virulence-associated genes, and resistance determinants. Most strains carried two large plasmids associated with environmental persistence and virulence, whereas the recent hospital isolate 19S, belonging to the ST11 group, carried two alternative plasmids enriched in virulence and antibiotic resistance genes. All genomes demonstrated conserved DAM-associated adenine methylation at GATC motifs, partial DCM-mediated cytosine methylation at CCWGG motifs, and widespread adenine methylation at CAGAG motifs linked to type III RM system. In contrast, the type I RM system present in the majority of sequenced strains was suppressed under laboratory growth conditions and remained active only in strain 19S, possibly due to mutations identified in the hsdM gene that may have released this methyltransferase from suppression. Novel epigenetic modification signals involving cytosine and guanine in replichore-biased tandem repeats were also identified. ConclusionsS. enterica strains circulating in Kazakhstan exhibit substantial genomic and epigenetic diversity associated with different survival and transmission strategies. DNA methylation profiling provided additional insights beyond conventional MLST genotyping and identified strain 19S as a promising model for future studies of epigenetic regulation in bacterial virulence and adaptation mediated through genomic DNA methylation.

genomics↗

bioRxiv2025

Application of long-read sequencing for genotyping, epigenetic profiling and surveillance of Yersinia pestis isolates from natural foci and disease outbreaks in Central Asia

This study explores the application of long-read sequencing technologies for genotyping, epigenetic profiling, and epidemiological monitoring of Yersinia pestis isolates obtained from natural foci in Central Asia and previous zoonotic outbreaks. Computational tools for genome assembly and genotyping were developed, enabling high-precision identification of both chromosomal and plasmid sequences, including the small cryptic pCKF plasmid. SNP-based genotyping distinguished the major Y. pestis biovars (Antiqua, Medievalis and non-main) and revealed cluster-specific diversity among Medievalis (MED) isolates, identifying a group of strains particularly prone to transmission from rodents to domestic animals and humans, which can be facilitated by the plasmid pCKF. Specific genomic polymorphisms were identified in sub-clades of MED isolates, which allow their identification with high precision. Additionally, comparative epigenomic analysis uncovered strain-specific cytosine methylation patterns at cgGATCG motifs, which may be linked to genome function regulation and adaptation to different hosts and environments. These findings demonstrate the effectiveness of long-read sequencing technologies in revealing both genetic and epigenetic features of bacterial pathogens, contributing to our understanding of the evolutionary mechanisms underlying the emergence and spread of this especially dangerous infection.

microbiology↗

bioRxiv2020

Comparison of transcriptional responses of three multidrug resistant model microorganisms, Staphylococcus aureus ATCC BAA-39, Escherichia coli ATCC BAA-196 and Acinetobacter baumannii ATCC BAA-1790, on exposure to iodine-containing nano-micelle drug FS-1

Iodine is one of the oldest antimicrobial agents. Till now there have been no reports on acquiring resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles, FS-1, against antibiotic resistant pathogens as a supplement to antibiotic therapy. The mechanisms of the action, however, remain unclear. The aim of this study was to perform a holistic analysis and comparison of gene regulation in three phylogenetically distant multidrug resistant reference strains representing pathogens associated with nosocomial infections from the ATCC culture collection: Escherichia coli BAA-196, Staphylococcus aureus BAA-39 and Acinetobacter baumannii BAA-1790. These cultures were treated by a 5 min exposure to sublethal concentrations of the iodine-containing drug FS-1 applied in the late lagging and the mid of the logarithmic growth phases. Complete genome sequences of these strains were obtained in the previous studies. Gene regulation was studied by total RNA extraction and Ion Torrent sequencing followed by mapping the RNA reads against the reference genome sequences and statistical processing of read counts using the DESeq2 algorithm. It was found that the treatment of bacteria with FS-1 profoundly affected the expression of many genes involved in central metabolic pathways; however, alterations of the gene expression profiles were species-specific and depended on the growth phase. Disruption of respiratory electron-transfer membrane complexes, increased penetrability of bacterial cell walls, osmotic and oxidative stresses leading to DNA damaging were the major factors influencing the treated bacteria. IMPORTANCEInfections caused by antibiotic resistant bacteria threaten the public health worldwide. Combinatorial therapy when antibiotics are administrated together with supplementary drugs improving susceptibility of pathogens to the regular antibiotics is considered as a promising way to overcome this problem. An induction of antibiotic resistance reversion by the iodine-containing nano-micelle drug FS-1 has been reported recently. This drug is currently under clinical trials in Kazakhstan against multidrug resistant tuberculosis. The effects of released iodine on metabolic and regulatory processes in bacterial cells remain unexplored. The current work provides an insight into gene regulation in the antibiotic resistant nosocomial reference strains treated with iodine-containing nanoparticles. This study sheds light on unexplored bioactivities of iodine and the mechanisms of its antibacterial effect when applied in sublethal concentrations. This knowledge will aid in the future design of new drugs against antibiotic resistant infections.

microbiology↗

bioRxiv2020

Differential gene expression and alternation of patterns of DNA methylation in the multidrug resistant strain Escherichia coli ATCC BAA-196 caused by iodine-containing nano-micelle drug FS-1 that induces antibiotic resistance reversion

BackgroundRecent studies showed promising results on application of iodine-containing nanomicelles, FS-1, against antibiotic resistant pathogens. The effect was studied on Escherichia coli ATCC BAA-196. Materials & methodsRNA sequencing for transcriptomics and the complete genome sequencing by SMRT PacBio RS II technology followed by genome assembly and methylomics study were performed. Results & conclusionsFS-1 treated E. coli showed an increased susceptibility to antibiotics ampicillin and gentamicin. The analysis of differential gene regulation showed that possible targets of iodine-containing particles are cell membrane fatty acids and proteins, particularly cytochromes, that leads to oxidative, osmotic and acidic stresses. Cultivation with FS-1 caused gene expression alterations towards anaerobic respiration, increased anabolism and inhibition of many nutrient uptake systems. Identification of methylated nucleotides showed an altered pattern in the FS-1 treated culture. Possible role of transcriptional and epigenetic modifications in the observed increase in susceptibility to gentamicin and ampicillin were discussed. Lay abstractNew approaches of combatting drug resistance infections are in demand as the development of new antibiotics is in a deep crisis. This study was set out to investigate molecular mechanisms of action of new iodine-containing nano-micelle drug FS-1, which potentially may improve the antibiotic therapy of drug resistant infections. Iodine is one of the oldest antimicrobials and until now there were no reports on development of resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles against antibiotic resistant pathogens as a supplement to antibiotic therapy. The mechanisms of action, however, remain unclear. The collection strain Escherichia coli ATCC BAA-196 showing an extended spectrum of resistance to beta-lactam and aminoglycoside antibiotics was used in this study as a model organism. Antibiotic resistance patterns, whole genomes and total RNA sequences of the FS-1 treated (FS) and negative control (NC) variants of E. coli BAA-196 were obtained and analyzed. FS culture showed an increased susceptibility to antibiotics associated with profound gene expression alterations switching the bacterial metabolism to anaerobic respiration, increased anabolism, osmotic stress response and inhibition of many nutrient uptake systems. Nucleotide methylation pattern were identified in FS and NC cultures. While the numbers of methylated sites in both genomes remained similar, some peculiar alterations were observed in their distribution along chromosomal and plasmid sequences.

genomics↗