Salmonella takes control: effector-driven manipulation of the host

Abstract

Salmonella pathogenesis relies upon the delivery of over thirty specialised effector proteins into the host cell via two distinct type III secretion systems. These effectors act in concert to subvert the host cell cytoskeleton, signal transduction pathways, membrane trafficking and pro-inflammatory responses. This allows Salmonella to invade non-phagocytic epithelial cells, establish and maintain an intracellular replicative niche and, in some cases, disseminate to cause systemic disease. This review focuses on the actions of the effectors on their host cell targets during each stage of Salmonella infection.

Figure 1

Schematic representation of the major stages underlying Salmonella infection. Salmonellae invade non-phagocytic cells by inducing membrane deformation and rearrangement of the underlying actin cytoskeleton (membrane ruffling), enclosing bacteria in intracellular phagosomal compartments termed Salmonella-containing vacuoles (SCVs). SCVs traffic towards the perinuclear region of the host cell and mature via selective interactions with the endocytic pathway. Once the SCV is positioned next to the Golgi apparatus, intracellular bacterial replication begins. This stage is characterised by the formation of SCV tubulovesicular structures called Salmonella-induced filaments (Sifs) and the accumulation of F-actin around the bacterial phagosome (actin nest). Chloride ion (Cl^-) secretion and polymorphonuclear leukocyte (PMN) transmigration contribute towards diarrhoea and intestinal inflammation. In addition, Salmonella manipulates specific host immune response pathways. Salmonella serovars associated with systemic disease are able to enter intestinal macrophages, inducing cell death as well as using them as a vehicle to disseminate to the liver and spleen via the bloodstream and lymphatic system. SPI-1 and SPI-2 effectors involved in each individual infection stage are indicated. Note that SPI-1 and SPI-2 effectors do not operate sequentially and independently of one another as previously thought. Instead, both subsets play key roles in SCV maturation, positioning and replication (Abbreviations: ER, endoplasmic reticulum; TGN, trans-Golgi network).