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PMID:21875964

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Citation

Arena, ET, Auweter, SD, Antunes, LC, Vogl, AW, Han, J, Guttman, JA, Croxen, MA, Menendez, A, Covey, SD, Borchers, CH and Finlay, BB (2011) The deubiquitinase activity of the Salmonella pathogenicity island 2 effector, SseL, prevents accumulation of cellular lipid droplets. Infect. Immun. 79:4392-400

Abstract

To cause disease, Salmonella enterica serovar Typhimurium requires two type III secretion systems that are encoded by Salmonella pathogenicity islands 1 and 2 (SPI-1 and -2). These secretion systems serve to deliver specialized proteins (effectors) into the host cell cytosol. While the importance of these effectors to promote colonization and replication within the host has been established, the specific roles of individual secreted effectors in the disease process are not well understood. In this study, we used an in vivo gallbladder epithelial cell infection model to study the function of the SPI-2-encoded type III effector, SseL. The deletion of the sseL gene resulted in bacterial filamentation and elongation and the unusual localization of Salmonella within infected epithelial cells. Infection with the ΔsseL strain also caused dramatic changes in host cell lipid metabolism and led to the massive accumulation of lipid droplets in infected cells. This phenotype was directly attributable to the deubiquitinase activity of SseL, as a Salmonella strain carrying a single point mutation in the catalytic cysteine also resulted in extensive lipid droplet accumulation. The excessive buildup of lipids due to the absence of a functional sseL gene also was observed in murine livers during S. Typhimurium infection. These results suggest that SseL alters host lipid metabolism in infected epithelial cells by modifying the ubiquitination patterns of cellular targets.

Links

PubMed PMC3257934 Online version:10.1128/IAI.05478-11

Keywords

Animals; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Endopeptidases/genetics; Endopeptidases/metabolism; Gallbladder/metabolism; Gallbladder/microbiology; Gene Expression Regulation, Bacterial; Genomic Islands/genetics; Genomic Islands/physiology; Lipid Metabolism/physiology; Liver/metabolism; Liver/microbiology; Mice; Salmonella Infections, Animal/microbiology; Salmonella typhimurium/enzymology; Salmonella typhimurium/genetics; Salmonella typhimurium/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

SALTY:SSEL

GO:0004843: ubiquitin-specific protease activity

ECO:0000314:

F

Figure 7

complete
CACAO 5488


See also

References

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