Post-translational weapons of microbial warfare: how bacterial effectors hijack host cell death and xenophagy.

The intricate interplay between pathogenic bacteria and host cellular processes represents a dynamic molecular battlefield during infection. Mammalian hosts employ two critical cell-autonomous defense mechanisms, regulated cell death (RCD) and xenophagy, to combat invading pathogens. RCD eliminates infected cells through programmed self-destruction, thereby removing bacterial replication niches and limiting pathogen spread. Concurrently, xenophagy sequesters intracellular bacteria within autophagosomes for subsequent lysosomal degradation. To subvert these host defenses, bacterial pathogens have evolved sophisticated effector proteins that mimic eukaryotic functional domains, enabling them to catalyze diverse post-translational modifications (PTMs) of host targets. While these PTM-mediated strategies are crucial for bacterial survival and persistence, current understanding of their specific mechanisms in modulating RCD and xenophagy remains fragmented. This review systematically examines the host–pathogen interaction landscape, with particular emphasis on how bacterial effector-driven PTMs disrupt these key defense pathways to establish infection. Elucidating the regulatory roles of bacterial PTMs in these processes is essential for advancing our knowledge of microbial pathogenesis and informing the development of innovative anti-infective therapies.