AraC/XylS family members, HilD and HilC, directly activate virulence gene expression independently of HilA in Salmonella typhimurium

Abstract

SummarySalmonella typhimurium is a Gram-negative enteric pathogen that can infect intestinal epithelial cells and induce inflammation of the intestinal mucosa. These processes are mediated by a type III secretion system (TTSS), which is encoded on Salmonella pathogenicity island 1 (SPI1). Previous studies showed that four SPI1-encoded transcriptional regulators, HilD, HilC, HilA and InvF, act in an ordered fashion to coordinately activate expression of the SPI1 TTSS. HilD and HilC derepress hilA transcription. HilA activates invF as well as SPI1 genes that encode components of the TTS apparatus. InvF then activates genes that encode proteins secreted by the SPI1 TTS apparatus. In this scheme, HilD and HilC indirectly activate expression of the SPI1 TTS apparatus and its secreted substrates by affecting hilA expression. Here, we report that HilD and HilC can also activate expression of a subset of SPI1 genes independently of HilA. Our studies show that HilD and HilC activate transcription of invF from a promoter that is far upstream of its HilA-dependent promoter. This activation is most probably through direct binding of HilD and HilC to sequences upstream and downstream of this alternative HilA-independent promoter. We conclude that HilD and HilC have a second role in SPI1 gene regulation that is separate from their role in co-ordinating expression of the SPI1 TTSS through hilA .

ppGpp-dependent Stationary Phase Induction of Genes on Salmonella Pathogenicity Island 1

“…5). Among the regulatory components, hilC/hilD has been shown to exert its regulatory effect by directly binding to a site upstream of hilAp (15,23,54). We observed under the standard growth condition that hilAp activity remained at the basal level in the HilC Ϫ or HilD Ϫ mutant background, although the defect was more severe in the HilD Ϫ mutant.…”

Lon Protease Activity Causes Down-Regulation of Salmonella Pathogenicity Island 1 Invasion Gene Expression after Infection of Epithelial Cells

“…The expression of hilA and hilD was examined because they encode important positive regulators of the invasive phenotype (6,58). We also examined the expression of hilC, carried on SPI-1, which increases the expression of hilA and activates the expression of the SPI-1 invF operon independently of hilA when overexpressed (1,23,55,58). The sicA gene, which encodes a chaperone, is the first gene in the sic-sip secreted-effector operon located on SPI-1, and its expression pattern should mimic that of hilA (15,16,42).…”

The Different Strategies Used by Salmonella to Invade Host Cells

“…Each of them binds directly to the hilA promoter and is able to activate its own expression. In fact, HilC, HilD and probably RtsA, act as derepressors of hilA transcription by counteracting the silencing exerted by nucleoidstructuring proteins such as H-NS or Hha (Akbar et al, 2003;Queiroz et al, 2011). The reason why HilC, HilD and RtsA play such an important role in T3SS-1 expression through hilA regulation is that they are at the integration point of a lot of signals that control SPI-1 expression ( Figure 4).…”

“…In this regulatory circuit, it is currently admitted that HilD has a predominant role whereas HilC and RtsA simply act as signal amplifiers. However, it has also been shown that these three regulators are also directly implicated in the regulation of others invasion genes (Akbar et al, 2003;Ellermeier & Slauch, 2004).…”