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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.
Mol Microbiol. 2005 Aug; 57(3):691-705.MM

Abstract

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.

Authors+Show Affiliations

Ellermeier CD
Department of Microbiology, University of Illinois, Urbana, IL, USA.
Ellermeier JR
No affiliation info available
Slauch JM
No affiliation info available

MeSH

AnimalsBacterial ProteinsGene Expression Regulation, BacterialHumansIntestine, SmallMiceMice, Inbred BALB CSalmonella Infections, AnimalSalmonella typhimuriumSpleenTrans-ActivatorsTranscription Factors

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16045614

Citation

Ellermeier, Craig D., et al. "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, vol. 57, no. 3, 2005, pp. 691-705.
Ellermeier CD, Ellermeier JR, Slauch JM. 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. Mol Microbiol. 2005;57(3):691-705.
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, 57(3), 691-705.
Ellermeier CD, Ellermeier JR, Slauch JM. 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. Mol Microbiol. 2005;57(3):691-705. PubMed PMID: 16045614.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ellermeier,Craig D, AU - Ellermeier,Jeremy R, AU - Slauch,James M, PY - 2005/7/28/pubmed PY - 2005/9/15/medline PY - 2005/7/28/entrez SP - 691 EP - 705 JF - Molecular microbiology JO - Mol Microbiol VL - 57 IS - 3 N2 - 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. SN - 0950-382X UR - https://www.unboundmedicine.com/medline/citation/16045614/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_ DB - PRIME DP - Unbound Medicine ER -