The Brucella type IV secretion system and effector proteins

Brucella spp. are Gram-negative, facultative intracellular bacteria responsible for brucellosis, a globally prevalent zoonosis affecting both humans and animals. The genus includes several pathogenic species which primarily infect mammals but can cause chronic infections in humans through accidental transmission. As for most intracellular pathogens, Brucella pathogenicity relies on its capacity to invade host cells, evade immune defenses, and establish a replicative niche within a specialized organelle, the Brucella-containing vacuole (BCV). Central to this process is the VirB Type IV secretion system (T4SS), a highly conserved molecular apparatus used to translocate effector proteins (EPs) into host cells. These EPs manipulate diverse cellular pathways to promote bacterial survival, replication, and dissemination. This review provides an updated overview of the structure and function of the T4SS, based on a comparison with recent structural information gained on conjugative systems. The current repertoire of known effectors and their roles in host-pathogen interactions are also detailed, highlighting progress made in their identification. Finally, we discuss possible functions of T4SS and speculate on the mechanisms of effector translocation based on insights from other intracellular pathogens or secretion systems.