Omeprazole antagonizes virulence and inflammation in Salmonella enterica-infected RAW264.7 cells

Abstract

The proton pump inhibitor omeprazole reduced the intracellular replication of Salmonella enterica serovar Typhimurium in RAW264.7 cells without affecting bacterial growth in vitro or the viability of the host cells. The mechanism was bacteriostatic and interfered with replication mediated by the virulence-associated SPI2 type III secretion system. The proton pump inhibitor bafilomycin A1, in contrast, mediated killing of intracellular bacteria and imposed a marked cytotoxicity on RAW264.7 cells. The two compounds also differentially affected the proinflammatory responses of the infected cells. Bafilomycin A1 enhanced nitric oxide production, whereas omeprazole delayed IκB degradation and blocked nitric oxide production and the secretion of proinflammatory cytokines. These results imply that omeprazole can be used to block the virulence factor-mediated intracellular replication of S. Typhimurium, and that its mechanism of growth inhibition is different from that mediated by bafilomycin A1. Copyright © 2009, American Society for Microbiology. All Rights Reserved.