PhoP-Induced Genes withinSalmonellaPathogenicity Island 1

Abstract

The invasive pathogen Salmonella enterica has evolved a sophisticated device that allows it to enter nonphagocytic host cells. This process requires the expression of Salmonella pathogenicity island 1 (SPI-1), which encodes a specialized type III protein secretion system (TTSS). This TTSS delivers a set of effectors that produce a marked rearrangement of the host cytoskeleton, generating a profuse membrane ruffling at the site of interaction, driving bacterial entry. It has been shown that the PhoP/PhoQ two-component system represses the expression of the SPI-1 machinery by down-regulating the transcription of its master regulator, HilA. In this work, we reveal the presence of a PhoP-activated operon within SPI-1. This operon is composed of the orgB and orgC genes, which encode a protein that interacts with the InvC ATPase and a putative effector protein of the TTSS, respectively. Under PhoP-inducing conditions, expression of this operon is directly activated by the phosphorylated form of the response regulator, which recognizes a PhoP box located at the -35 region relative to the transcription start site. Additionally, under invasion-inducing conditions, orgBC expression is driven both by the prgH promoter, induced by the SPI-1 master regulator HilA, and by the directly controlled PhoP/PhoQ promoter. Together, these results indicate that in contrast to the rest of the genes encompassed in the SPI-1 locus, orgBC is expressed during and after Salmonella entry into its host cell, and they suggest a role for the products of this operon after host cell internalization.