Salmonella SPI-2 Type III Secretion System Effectors: Molecular Mechanisms And Physiological Consequences  Elliott Jennings, Teresa L.M. Thurston, David W. Holden  Cell Host & Microbe  Volume 22, Issue 2, Pages 217-231 (August 2017) DOI: 10.1016/j.chom.2017.07.009 Copyright © 2017 Terms and Conditions

Figure 1 Distribution of SPI-2 T3SS Effectors across Different Samonella enterica Serovars (A) Genomic location of effector genes in serovar Typhimurium strain ATCC 14028. Where effector genes are within a pathogenicity island, the number of the pathogenicity island is stated. “P” denotes that the effector gene is in a prophage. (B) BLASTn searches, using the CDS from serovar Typhimurium strain ATCC 14028, were done to identify orthologous CDSs in the subject genomes. Orthologous CDS with ≥90% sequence coverage and ≥90% sequence identity were marked as “intact.” Orthologous CDS with premature stop codons, frameshifts, or changes to the start codon were marked as “HDC.” For subject genomes where an orthologous CDS was not identified or did not fulfill the criteria outlined above, the CDS was marked as “absent.” The number of isolates of each serovar included in the analysis is stated in brackets. Although pipA and gogA have been included here, SPI-2 T3SS-dependent translocation of PipA and GogA has not been shown. Abbreviations: CDS, coding DNA sequence; HDC, hypothetically disrupted coding DNA sequence. Figure is adapted and extended from Nuccio and Bäumler (2014). Cell Host & Microbe 2017 22, 217-231DOI: (10.1016/j.chom.2017.07.009) Copyright © 2017 Terms and Conditions

Figure 2 Interaction Partners of SPI-2 T3SS Effectors Abbreviations: SCV, Salmonella-containing vacuole; mMHCII, mature major histocompatibility class II; Ub, ubiquitin; p, phospho; PI(4)P, phosphatidylinositol 4-phosphate. Cell Host & Microbe 2017 22, 217-231DOI: (10.1016/j.chom.2017.07.009) Copyright © 2017 Terms and Conditions

Figure 3 Cell-Type-Specific Functions of SPI-2 T3SS Effectors (A) In Salmonella-infected epithelial cells, Salmonella-containing vacuoles (SCVs) form a microcolony in a juxtanuclear position and are tethered to the Golgi network by two transmembrane effectors, SseF and SseG. As the SCV membrane partitions around dividing vacuolar Salmonella, each bacterium is frequently enclosed into an individual vacuole. This process requires SifA and SteA. Additionally, SifA, PipB2, SseJ, and SopD2 function in the formation and elongation of tubular extensions of the SCV called Salmonella-induced tubules (SITs). SteC is required for the formation of an F-actin meshwork that surrounds the microcolony, whereas SseL prevents the accumulation of lipid droplets in the cytoplasm. (B) SseL, SseK1, and SseK3 modulate cell death in Salmonella-infected macrophages. SseK1 and SseK3 inhibit necroptotic cell death, whereas SseL seems to induce cell death at late time points after phagocytosis. (C) SifA inhibits the retrograde trafficking of mannose-6-phosphate receptors (MPRs) from late endosomes and lysosomes to the trans-Golgi network. This leads to the secretion of lysosomal hydrolases and a reduction of lysosomal potency. SifA is also required for the recruitment of late endosomes and lysosomes to the SCV as a potential source of nutrients and membrane. SseL inhibits autophagic clearance of cytoplasmic aggregates that form during Salmonella infection, and SpvB inhibits F-actin polymerization. A subset of effectors including GogB, GtgA, SseK1, SseK2, SseK3, SspH1, SpvC, and SpvD inhibit innate immune signaling. (D) In Salmonella-infected dendritic cells, the transmembrane effector SteD is required for the depletion of surface mature major histocompatibility class II (mMHCII). This inhibits antigen presentation and T-cell proliferation. Furthermore, SseI prevents the directional migration of dentritic cells. Effector functions are shown in the cell type in which they have been described; however, the same function might be carried out in different cell types. Abbreviations: SCV, Salmonella-containing vacuole; SIT, Salmonella-induced tubule; MPR, mannose-6-phosphate receptor; mMHCII, mature major histocompatibility class II; PRRs, pattern recognition receptors. Cell Host & Microbe 2017 22, 217-231DOI: (10.1016/j.chom.2017.07.009) Copyright © 2017 Terms and Conditions