Oxygen-dependent regulation of SPI1 type three secretion system by small RNAs in Salmonella enterica serovar Typhimurium

Kyungsub Kim, Yekaterina A. Golubeva, Carin Vanderpool, James McClurg Slauch

Research output: Contribution to journalArticle

Abstract

Salmonella Typhimurium induces inflammatory diarrhea and uptake into intestinal epithelial cells using the Salmonella pathogenicity island 1 (SPI1) type III secretion system (T3SS). Three AraC-like regulators, HilD, HilC and RtsA, form a feed-forward regulatory loop that activates transcription of hilA, encoding the activator of the T3SS structural genes. Many environmental signals and regulatory systems are integrated into this circuit to precisely regulate SPI1 expression. A subset of these regulatory factors affects translation of hilD, but the mechanisms are poorly understood. Here, we identified two sRNAs, FnrS and ArcZ, which repress hilD translation, leading to decreased production of HilA. FnrS and ArcZ are oppositely regulated in response to oxygen, one of the key environmental signals affecting expression of SPI1. Mutational analysis demonstrates that FnrS and ArcZ bind to the hilD mRNA 5′ UTR, resulting in translational repression. Deletion of fnrS led to increased HilD production under low-aeration conditions, whereas deletion of arcZ abolished the regulatory effect on hilD translation aerobically. The fnrS arcZ double mutant has phenotypes in a mouse oral infection model consistent with increased expression of SPI1. Together, these results suggest that coordinated regulation by these two sRNAs maximizes HilD production at an intermediate level of oxygen.

Original languageEnglish (US)
Pages (from-to)570-587
Number of pages18
JournalMolecular Microbiology
Volume111
Issue number3
DOIs
StatePublished - Mar 2019

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Genomic Islands
Salmonella enterica
Salmonella
RNA
Oxygen
5' Untranslated Regions
Salmonella typhimurium
Diarrhea
Epithelial Cells
Phenotype
Messenger RNA
Serogroup
Type I Secretion Systems
Infection
Genes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Oxygen-dependent regulation of SPI1 type three secretion system by small RNAs in Salmonella enterica serovar Typhimurium. / Kim, Kyungsub; Golubeva, Yekaterina A.; Vanderpool, Carin; Slauch, James McClurg.

In: Molecular Microbiology, Vol. 111, No. 3, 03.2019, p. 570-587.

Research output: Contribution to journalArticle

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