The Salmonella Effector Protein SopB Protects Epithelial Cells from Apoptosis by Sustained Activation of Akt

• Published in: The Journal of biological chemistry 2005-03, Vol.280 (10), p.9058-9064
• Main Authors: Knodler, Leigh A., Finlay, B. Brett, Steele-Mortimer, Olivia
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Bacterial Proteins - metabolism; Camptothecin - pharmacology; Caspase 3; Caspases - drug effects; Caspases - metabolism; Cell Line; Epithelial Cells - cytology; Epithelial Cells - pathology; Epithelial Cells - physiology; HeLa Cells; Humans; Intestinal Mucosa - cytology; Intestinal Mucosa - physiology; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Rats; RNA, Small Interfering - genetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M412588200

Invasion of epithelial cells by Salmonella enterica is mediated by bacterial “effector” proteins that are delivered into the host cell by a type III secretion system. Although primarily known for their roles in actin rearrangements and membrane ruffling, translocated effectors also affect host cell processes that are not directly associated with invasion. Here, we show that SopB/SigD, an effector with phosphoinositide phosphatase activity, has anti-apoptotic activity in Salmonella-infected epithelial cells. Salmonella induced the sustained activation of Akt/protein kinase B, a pro-survival kinase, in a SopB-dependent manner. Failure to activate Akt resulted in increased levels of apoptosis after infection with a sopB deletion mutant (ΔsopB). Furthermore, cells infected with wild type bacteria, but not the ΔsopB strain, were protected from camptothecin-induced cleavage of caspase-3 and subsequent apoptosis. The anti-apoptotic activity of SopB was dependent on its phosphatase activity, because a catalytically inactive mutant was unable to protect cells from the effects of camptothecin. Finally, small interfering RNA was used to demonstrate the essential role of Akt in SopB-mediated protection against apoptosis. These results provide new insights into the mechanisms of apoptosis and highlight how bacterial effectors can intercept signaling pathways to manipulate host responses.