Salmonellae interactions with host processes

Key Points Salmonella spp. deliver effector proteins into host cells to promote replication and survival. Effector proteins that are translocated by the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (T3SS) are important for bacterial invasion into non-phagocytic cells. Effector proteins that are delivered by the SPI-2 T3SS modify the Salmonella -containing vacuole, associated endosomal membranes and associated proteins, all of which promote intracellular replication. Induction of inflammation enhances extracellular growth of salmonellae and enables them to outcompete the gut microbiota. Interplay between the host response pathways of autophagy and pyroptosis is involved in the detection of intracellular Salmonella spp. Distinct functions for many of the Salmonella effector proteins are not fully understood, and it is likely that many of their functions will only be elucidated when their activities are studied in the context of other effectors and are considered in a spatiotemporal context within the host. In this Review, Miller and colleagues discuss the arsenal of effector proteins that salmonellae use to manipulate their animal hosts, in addition to the host response to these infections. The authors also discuss the challenges ahead for unravelling the mechanistic details of effector function. Salmonellae invasion and intracellular replication within host cells result in a range of diseases, including gastroenteritis, bacteraemia, enteric fever and focal infections. In recent years, considerable progress has been made in our understanding of the molecular mechanisms that salmonellae use to alter host cell physiology; through the delivery of effector proteins with specific activities and through the modulation of defence and stress response pathways. In this Review, we summarize our current knowledge of the complex interplay between bacterial and host factors that leads to inflammation, disease and, in most cases, control of the infection by its animal hosts, with a particular focus on Salmonella enterica subsp. enterica serovar Typhimurium. We also highlight gaps in our knowledge of the contributions of salmonellae and the host to disease pathogenesis, and we suggest future avenues for further study.