Reprogramming host histone modifications by bacterial pathogens

Bacterial pathogens have evolved sophisticated strategies to manipulate host cellular processes, ensuring survival, replication, and long-term persistence. Beyond classical immune signaling, emerging evidence highlights the central role of epigenetic regulation in host-pathogen interactions. Pathogens exploit host chromatin through 2 principal mechanisms: (1) direct modification of histones by bacterial effector proteins with intrinsic enzymatic activities and (2) indirect modulation of host epigenetic states through alterations in signaling pathways or cellular metabolism. These interventions alter post-translational histone modifications-acetylation, methylation, phosphorylation, and lactylation-thereby reshaping transcriptional programs to suppress antimicrobial responses, promote immune tolerance, or establish persistent infection. This review summarizes recent advances in understanding the dynamic interplay between bacterial virulence and host chromatin regulation, highlighting epigenetic reprogramming as a key determinant of infection outcomes.