The Type III Secretion System Effector SeoC of Salmonella entericasubsp. salamaeand S. entericasubsp. arizonaeADP-Ribosylates Src and Inhibits Opsonophagocytosis

Autor: Pollard, Dominic J., Young, Joanna C., Covarelli, Valentina, Herrera-León, Silvia, Connor, Thomas R., Fookes, Maria, Walker, Danielle, Echeita, Aurora, Thomson, Nicholas R., Berger, Cedric N., Frankel, Gad
Zdroj: Infection and Immunity; September 2016, Vol. 84 Issue: 12 p3618-3628, 11p
Abstrakt: ABSTRACTSalmonellaspecies utilize type III secretion systems (T3SSs) to translocate effectors into the cytosol of mammalian host cells, subverting cell signaling and facilitating the onset of gastroenteritis. In this study, we compared a draft genome assembly of Salmonella entericasubsp. salamaestrain 3588/07 against the genomes of S. entericasubsp. entericaserovar Typhimurium strain LT2 and Salmonella bongoristrain 12419. S. entericasubsp. salamaeencodes the Salmonellapathogenicity island 1 (SPI-1), SPI-2, and the locus of enterocyte effacement (LEE) T3SSs. Though several key S. Typhimurium effector genes are missing (e.g., avrA, sopB, and sseL), S. entericasubsp. salamaeinvades HeLa cells and contains homologues of S. bongori sboKand sboC, which we named seoC. SboC and SeoC are homologues of EspJ from enteropathogenic and enterohemorrhagic Escherichia coli(EPEC and EHEC, respectively), which inhibit Src kinase-dependent phagocytosis by ADP-ribosylation. By screening 73 clinical and environmental Salmonellaisolates, we identified EspJ homologues in S. bongori, S. entericasubsp. salamae, and Salmonella entericasubsp. arizonae. The β-lactamase TEM-1 reporter system showed that SeoC is translocated by the SPI-1 T3SS. All the SalmonellaSeoC/SboC homologues ADP-ribosylate Src E310 in vitro. Ectopic expression of SeoC/SboC inhibited phagocytosis of IgG-opsonized beads into Cos-7 cells stably expressing green fluorescent protein (GFP)-FcγRIIa. Concurrently, S. entericasubsp. salamaeinfection of J774.A1 macrophages inhibited phagocytosis of beads, in a seoC-dependent manner. These results show that S. bongori, S. entericasubsp. salamae, and S. entericasubsp. arizonaeshare features of the infection strategy of extracellular pathogens EPEC and EHEC and shed light on the complexities of the T3SS effector repertoires of Enterobacteriaceae.
Databáze: Supplemental Index