Correction: The role of coupled positive feedback in the expression of the SPI1 type three secretion system in Salmonella.

Supreet Saini, Jeremy R. Ellermeier, James M. Slauch, Christopher V. Rao

Research output: Contribution to journalArticle

Abstract

Salmonella enterica serovar Typhimurium is a common food-borne pathogen that induces inflammatory diarrhea and invades intestinal epithelial cells using a type three secretion system (T3SS) encoded within Salmonella pathogenicity island 1 (SPI1). The genes encoding the SPI1 T3SS are tightly regulated by a network of interacting transcriptional regulators involving three coupled positive feedback loops. While the core architecture of the SPI1 gene circuit has been determined, the relative roles of these interacting regulators and associated feedback loops are still unknown. To determine the function of this circuit, we measured gene expression dynamics at both population and single-cell resolution in a number of SPI1 regulatory mutants. Using these data, we constructed a mathematical model of the SPI1 gene circuit. Analysis of the model predicted that the circuit serves two functions. The first is to place a threshold on SPI1 activation, ensuring that the genes encoding the T3SS are expressed only in response to the appropriate combination of environmental and cellular cues. The second is to amplify SPI1 gene expression. To experimentally test these predictions, we rewired the SPI1 genetic circuit by changing its regulatory architecture. This enabled us to directly test our predictions regarding the function of the circuit by varying the strength and dynamics of the activating signal. Collectively, our experimental and computational results enable us to deconstruct this complex circuit and determine the role of its individual components in regulating SPI1 gene expression dynamics.

Original languageEnglish (US)
JournalPLoS pathogens
Volume6
Issue number8
DOIs
StatePublished - 2010
Externally publishedYes

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Genomic Islands
Salmonella
Gene Regulatory Networks
Gene Expression
Type I Secretion Systems
Salmonella enterica
Transcriptional Activation
Cues
Diarrhea
Theoretical Models
Epithelial Cells
Food

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Correction : The role of coupled positive feedback in the expression of the SPI1 type three secretion system in Salmonella. / Saini, Supreet; Ellermeier, Jeremy R.; Slauch, James M.; Rao, Christopher V.

In: PLoS pathogens, Vol. 6, No. 8, 2010.

Research output: Contribution to journalArticle

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