Delineation of the Salmonella Typhimurium HilA regulon through genome-wide location and transcript analysis

Centre of Microbial and Plant Genetics, K.U.Leuven, Kasteelpark Arenberg 20, 3001 Leuven, Belgium; ESAT-SCD, K.U.Leuven, Kasteelpark Arenberg 10, 3001 Leuven, Belgium; Sidney Kimmel Cancer Center, 10835 Altman Row, San Diego, California 92121

^* To whom correspondence should be addressed. Email: sigrid.dekeersmaecker{at}biw.kuleuven.be.

	Abstract

The Salmonella enterica serovar Typhimurium HilA protein is the key regulator for the invasion of epithelial cells. By combining genome-wide location and transcript analysis, the HilA dependent regulon has been delineated. Under invasion inducing conditions, HilA binds to most of the known target genes and a number of new target genes. The sopB, sopE and sopA genes, encoding effector proteins secreted by the type three secretion system on Salmonella pathogenicity island 1 (SPI-1), were identified both as being bound by HilA and differentially regulated in an HilA mutant. This suggests a cooperative role for HilA and InvF in the regulation of SPI-1 secreted effectors. Also siiA, the first gene of SPI-4, is both bound by HilA and differentially regulated in an HilA mutant, thus linking this pathogenicity island to the invasion key regulator. Finally, the interactions of HilA with the SPI-2 secretion system gene ssaH and the flagellar gene flhD imply a repressor function for HilA under invasion inducing conditions.