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Cited by 258

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HilD, HilC and RtsA constitute a feed forward loop that controls expression of the SPI1 type three secretion system regulator hilA in Salmonella enterica serovar Typhimurium

Ellermeier, Craig D., Ellermeier, Jeremy R., Slauch, James M.·2005·Molecular Microbiology

Abstract

Summary: Salmonella enterica serovar Typhimurium invades intestinal epithelial cells using a type three secretion system (TTSS) encoded on Salmonella Pathogenicity Island 1 (SPI1). The SPI1 TTSS injects effector proteins into the cytosol of host cells where they promote actin rearrangement and engulfment of the bacteria. We previously identified RtsA, an AraC‐like protein similar to the known HilC and HilD regulatory proteins. Like HilC and HilD, RtsA activates expression of SPI1 genes by binding upstream of the master regulatory gene hilA to induce its expression. HilA activates the SPI1 TTSS structural genes. Here we present evidence that hilA expression, and hence the SPI1 TTSS, is controlled by a feedforward regulatory loop. We demonstrate that HilC, HilD and RtsA are each capable of independently inducing expression of the hilC, hilD and rtsA genes, and that each can independently activate hilA. Using competition assays in vivo, we show that each of the hilA regulators contribute to SPI1 induction in the intestine. Of the three, HilD has a predominant role, but apparently does not act alone either in vivo or in vitro to sufficiently activate SPI1. The two‐component regulatory systems, SirA/BarA and OmpR/EnvZ, function through HilD, thus inducing hilC, rtsA and hilA. However, the two‐component systems are not responsible for environmental regulation of SPI1. Rather, we show that ‘SPI1 inducing conditions’ cause independent activation of the rtsA, hilC and hilD genes in the absence of known regulators. Our model of SPI1 regulation provides a framework for future studies aimed at understanding this complicated regulatory network.

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Metadata

Authors
Ellermeier, C. D., Ellermeier, J. R., & Slauch, J. M.
Venue
Molecular Microbiology
Publisher
Wiley
Published
2005-06-30
Volume
57
Issue
3
Pages
691-705
ISSN
  • 0950-382X (ISSN-L)
  • 1365-2958
OpenAlex
W1849830312
Cited by
258
References
69
FWCI
4.71
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: HilD, HilC and RtsA constitute a feed forward loop that controls expression of the SPI1 type three secretion system regulator hilA in Salmonella enterica serovar Typhimurium. https://app.cochat.ai/papers/10.1111/j.1365-2958.2005.04737.x
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Ellermeier, C. D., Ellermeier, J. R., & Slauch, J. M. (2005). HilD, HilC and RtsA constitute a feed forward loop that controls expression of the SPI1 type three secretion system regulator hilA in Salmonella enterica serovar Typhimurium. Molecular Microbiology. https://doi.org/10.1111/j.1365-2958.2005.04737.x

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