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Journal of Bacteriology, July 2000, p. 4077-4086, Vol. 182, No. 14
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A PhoP-Regulated Outer Membrane Protease of Salmonella enterica Serovar Typhimurium Promotes Resistance to Alpha-Helical Antimicrobial Peptides

Tina Guina,¹ Eugene C. Yi,² Houle Wang,^2, Murray Hackett,² and Samuel I. Miller^1,3,*

Departments of Microbiology,¹ Medicine,³ and Medicinal Chemistry,² University of Washington, Seattle, Washington 98195

Received 7 March 2000/Accepted 2 May 2000

The outer membrane protein contents of Salmonella enterica serovar Typhimurium strains with PhoP/PhoQ regulon mutations were compared by two-dimensional gel electrophoresis. At least 26 species of outer membrane proteins (OMPs) were identified as being regulated by PhoP/PhoQ activation. One PhoP/PhoQ-activated OMP was identified by semiautomated tandem mass spectrometry coupled with electronic database searching as PgtE, a member of the Escherichia coli OmpT and Yersinia pestis Pla family of outer membrane proteases. Salmonella PgtE expression promoted resistance to alpha-helical cationic antimicrobial peptides (-CAMPs). Strains expressing PgtE cleaved C18G, an 18-residue -CAMP present in culture medium, indicating that protease activity is likely to be the mechanism of OmpT-mediated resistance to -CAMPs. PhoP/PhoQ did not regulate the transcription or export of PgtE, indicating that another PhoP/PhoQ-dependent mechanism is required for PgtE outer membrane localization. PgtE is a posttranscriptionally regulated component of the PhoP/PhoQ regulon that contributes to Salmonella resistance to innate immunity.

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^* Corresponding author. Mailing address: Dept. of Microbiology, University of Washington, HSB K-140, Box 357710, Seattle, WA 98195. Phone: (206) 616-5107. Fax: (206) 616-4295. E-mail: millersi{at}u.washington.edu.

Present address: Bruker Daltonics, Billerica, MA 01821.

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Journal of Bacteriology, July 2000, p. 4077-4086, Vol. 182, No. 14
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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