A PhoP-regulated outer membrane protease of Salmonella enterica serovar typhimurium promotes resistance to alpha-helical antimicrobial peptides

The outer membrane protein contents of Salmonella enterica serovar Typhimur ium strains with PhoP/PhoQ regulon mutations were compared by two-dimension al gel electrophoresis. At least 26 species of outer membrane proteins (OMP s) were identified as being regulated by PhoP/PhoQ activation. One PhoP/Pho Q-activated OMP was identified by semiautomated tandem mass spectrometry co upled with electronic database searching as PgtE, a member of the Escherich ia coli OmpT and Yersinia pestis Pla family of outer membrane proteases, Sa lmonella PgtE expression promoted resistance to alpha-helical cationic anti microbial peptides (alpha-CAMPs). Strains expressing PgtE cleaved C18G, an 18-residue alpha-CAMP present in culture medium, indicating that protease a ctivity is likely to be the mechanism of OmpT-mediated resistance to alpha- CAMPs. PhoP/PhoQ did not regulate the transcription or export of PgtE, indi cating that another PhoP/PhoQ-dependent mechanism is required for PgtE oute r membrane localization. PgtE is a posttranscriptionally regulated componen t of the PhoP/PhoQ regulon that contributes to Salmonella resistance to inn ate immunity.