iProXProteomicsQian LiHomo SapiensMus MusculusBurkholderia Pseudomallei K96243http://www.iprox.org/page/project.html?id=IPX0018866000liqianjane@tmmu.edu.cnDepartment of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, ChinaiProXfalseA Burkholderia nucleomodulin hijacks the NuRD complex to epigenetically suppress efferocytosisBurkholderia pseudomallei, the facultative intracellular pathogen that causes life-threatening melioidosis, delivers virulence effectors through secretion systems to subvert host-cell immunity, yet whether it deploys nuclear-targeted effectors to reprogram host immune responses remains unclear. Here, we identify BapC as a type III secretion system nucleomodulin that suppresses macrophage efferocytosis through epigenetic reprogramming. Mechanistically, BapC enters the host nucleus through an Asp95-dependent interaction with KPNB1. Nuclear BapC engages the Nucleosome Remodeling and Deacetylase (NuRD) complex to drive histone H3K18 deacetylation and repress efferocytosis-related genes. This epigenetic suppression impairs efferocytotic clearance of apoptotic cells by macrophages and promotes bacterial survival. Pharmacological inhibition of HDAC1/2, the deacetylase subunits of NuRD, restores efferocytosis and protects against lethal infection. Together, our study reveals how B. pseudomallei exploits a bacterial nucleomodulin to hijack a host chromatin corepressor complex and suppress innate immune clearance, suggesting HDAC inhibition as a potential host-directed therapeutic strategy for melioidosis.Fri Aug 07 00:00:00 GMT+01:00 2026PXD082311100902725609606