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Antimicrobial Agents and Chemotherapy, June 2009, p. 2402-2409, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.01483-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Omeprazole Antagonizes Virulence and Inflammation in Salmonella enterica-Infected RAW264.7 Cells{triangledown}

Speranta Puiac,1 Aurel Negrea,1 Agneta Richter-Dahlfors,2 Laura Plant,1 and Mikael Rhen1*

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, SE-171 77 Stockholm, Sweden,1 Department of Neuroscience, Karolinska Institutet, Retzius väg 8, SE-171 77 Stockholm, Sweden2

Received 6 November 2008/ Returned for modification 24 January 2009/ Accepted 15 March 2009

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 I{kappa}B 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.

* Corresponding author. Mailing address: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, SE-171 77 Stockholm, Sweden. Phone: 46-8-524 8 6252. Fax: 46-8-330498. E-mail: Mikael.Rhen{at}ki.se

{triangledown} Published ahead of print on 23 March 2009.

Antimicrobial Agents and Chemotherapy, June 2009, p. 2402-2409, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.01483-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Negrea, A., Bjur, E., Puiac, S., Ygberg, S. E., Aslund, F., Rhen, M. (2009). Thioredoxin 1 Participates in the Activity of the Salmonella enterica Serovar Typhimurium Pathogenicity Island 2 Type III Secretion System. J. Bacteriol. 191: 6918-6927 [Abstract] [Full Text]  


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