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.