Brucella-driven host N-glycome remodeling controls infection

Many powerful methods have been employed to elucidate the global transcriptomic, proteomic, or metabolic responses to pathogen-infected host cells. However, the host glycome responses to bacterial infection remain largely unexplored, and hence, our understanding of the molecular mechanisms by which bacterial pathogens manipulate the host glycome to favor infection remains incomplete. Here, we address this gap by performing a systematic analysis of the host glycome during infection by the bacterial pathogen Brucella spp. that cause brucellosis. We discover, surprisingly, that a Brucella effector protein (EP) Rhg1 induces global reprogramming of the host cell N-glycome by interacting with components of the oligosaccharide transferase complex that controls N-linked protein glycosylation, and Rhg1 regulates Brucella replication and tissue colonization in a mouse model of brucellosis, demonstrating that Brucella exploits the EP Rhg1 to reprogram the host N-glycome and promote bacterial intracellular parasitism, thereby providing a paradigm for bacterial control of host cell infection. [Display omitted] •B. melitensis Rhg1 is an effector protein secreted via its type IV secretion system•Rhg1 interacts with components of the host OST complex and the ER SEC61 translocon•Rhg1 expression impairs host protein N-glycosylation and reduces glycan abundance•Rhg1 regulates B. melitensis infection in a mouse model The stealthy bacterial pathogen Brucella melitensis causes brucellosis, a zoonosis of global importance. Cabello et al. demonstrate that the Brucella effector Rhg1 reprograms the host N-glycome to support its intracellular lifestyle via interacting with the host OST complex and ER SEC61 translocon to manipulate N-glycosylation and host functions.