Salmonella pathogenicity island 4-mediated adhesion is coregulated with invasion genes in Salmonella enterica

Salmonella pathogenicity island 4 (SP14) encodes a type I secretion system and the cognate substrate protein, SiiE. We have recently demonstrated that SiiE is a giant nonfimbrial adhesin involved in the adhesion of Salmonella enterica serovar Typhimurium to polarized epithelial cells. We also observed that under in vitro culture conditions, the synthesis and secretion of SiiE coincided with the activation of Salmonella invasion genes. These observations prompted us to investigate the regulation of SP14 genes in detail. A novel approach for the generation of reporter gene fusions was employed to generate single-copy chromosomal fusions to various genes within SP14, and the expression of these fusions was investigated. We analyzed the regulation of SP14 genes and the roles of various regulatory systems for SP14 expression. Our data show that the expression of SP14 genes is coregulated with SPI1 invasion genes by the global regulator SirA. Expression of a SP14 gene was also reduced in the absence of HiIA, the central local regulator of SPI1 gene expression. Both SirA and HilA functions were required for the secretion of SiiE and the SP14-mediated adhesion. Our data demonstrate that SP14-mediated adhesion, as well as SPI1-mediated invasion, are tightly coregulated by the same regulatory circuits and induced under similar environmental conditions.