Staphylococcus aureus α-hemolysin induces DNA methylation changes in human Th1 cells

α-Hemolysin is one of the most dangerous virulence factors produced by Staphylococcus aureus. Among the immune cells that respond to this pathogenic bacterium, Th1 lymphocytes play a critical role. In our study, we investigated the impact of α-hemolysin on the methylation of the Th1 cell genome. Our findings revealed that α-hemolysin upregulates HELLS and DNMT3A expression while downregulating DNMT3L expression at the protein level. Whole-genome bisulfite sequencing analysis revealed significant alterations in DNA methylation, particularly in regions outside CpG sequences. These results suggest that bacterial proteins can act as potent epigenetic modulators in human cells, influencing their activity, plasticity, and phenotype.