Subversive Salmonella: Salmonella is one of the most intensively studied bacterial pathogens. The Salmonella -containing vacuole (SCV) has a paradoxical lysosome-like composition: On one hand, the SCV membrane is highly enriched in lysosomal membrane glycoproteins and SCVs are accessible to endolysosomal content, but on the other hand, SCV lumen is relatively devoid of lysosomal hydrolytic enzymes that are delivered by the mannose-6-phosphate receptor pathway. McGourty et al. (p. 963 ) resolve this paradox by showing that the Salmonella effector SifA interferes with the trafficking of mannose-6-phosphate receptors. This causes misrouting and secretion of lysosomal enzymes and reduces the hydrolytic activity of lysosomes. Intracellular growth of Salmonella was reduced in cells with enhanced lysosomal enzyme activity.

Type III secretion (T3S) systems are widespread among Gram‐negative bacteria pathogenic for animals and plants, including Yersinia spp., Salmonella spp., Shigella spp., enteropathogenic Escherichia coli, enterohaemorrhagic E. coli, or Pseudomonas spp. T3S systems allow bacteria to inject virulence proteins, called T3S effectors, into the cytosol of their eukaryotic host cells. These virulence factors will paralyze or reprogram the eukaryotic cell to the benefit of the pathogen. T3S effectors display a large repertoire of biochemical activities and modulate the function of crucial host regulatory molecules such as small guanosine triphosphate (GTP)‐binding proteins, mitogen‐activated protein kinases (MAPKs), nuclear factor (NF)‐κB, or phosphoinositides. The activity of T3S effectors allows bacteria, for example, to invade non‐phagocytic cells or to inhibit phagocytosis, to downregulate or promote pro‐inflammatory responses, to induce apoptosis, to prevent autophagy, or to modulate intracellular trafficking. In this review, we present the most recent advances in the understanding of the mode of action of T3S effectors. We highlight the biochemical activities of these eukaryotic‐like bacterial proteins that are shared among pathogens carrying T3S systems and the sequence, structural and functional resemblances between T3S effectors and eukaryotic proteins.

Many pathogenic bacteria use a type III secretion nanomachine (an injectisome) to deliver virulence proteins into the cytosol of their eukaryotic host cells. Most injectisomes possess a stiff needlelike structure of a genetically defined length. We found that a minimal needle length was required for efficient functioning of the Yersinia enterocolitica injectisome. This minimal needle length correlated with the length of the major adhesin at the bacterial surface. The needle may be required for triggering type III secretion, and its length may have evolved to match specific structures at the bacterial and host cell surfaces.

Salmonella enterica are facultative intracellular bacterial pathogens that proliferate within host cells in a membrane-bounded compartment, the Salmonella-containing vacuole (SCV). Intracellular replication of Salmonella is mediated by bacterial effectors translocated on to the cytoplasmic face of the SCV membrane by a type III secretion system. Some of these effectors manipulate the host endocytic pathway, resulting in the formation in epithelial cells of tubules enriched in late endosomal markers, known as Salmonella-induced filaments (SIFs). However, much less is known about possible interference of Salmonella with the secretory pathway. Here, a small-interference RNA screen revealed that secretory carrier membrane proteins (SCAMPs) 2 and 3 contribute to the maintenance of SCVs in the Golgi region of HeLa cells. This is likely to reflect a function of SCAMPs in vacuolar membrane dynamics. Moreover, SCAMP3, which accumulates on the trans-Golgi network in uninfected cells, marked tubules induced by Salmonella effectors that overlapped with SIFs but which also comprised distinct tubules lacking late endosomal proteins. We propose that SCAMP3 tubules reflect a manipulation of specific post-Golgi trafficking that might allow Salmonella to acquire nutrients and membrane, or to control host immune responses.