Omeprazole antagonizes virulence and inflammation in Salmonella enterica-infected RAW264.7 cells.
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 A(1), 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 A(1) enhanced nitric oxide production, whereas omeprazole delayed IkappaB 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 A(1).
Puiac
Speranta
S
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, SE-171 77 Stockholm, Sweden.
Negrea
Aurel
A
Richter-Dahlfors
Agneta
A
Plant
Laura
L
Rhen
Mikael
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D044404:Genomic Islands; D018942:Macrolides / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D009853:Omeprazole / Q000494:pharmacology*; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D019779:Salmonella enterica / Q000187:drug effects* / Q000254:growth & development; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism; D014774:Virulence
D000893:Anti-Inflammatory Agents; D018942:Macrolides; D054328:Proton Pump Inhibitors; D009569:Nitric Oxide; C040929:bafilomycin A1; D052247:Nitric Oxide Synthase Type II; D009853:Omeprazole