Control of a Salmonella virulence operon by proline-charged tRNA Pro

Eun Jin Lee, Jeongjoon Choi, Eduardo A. Groisman

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The intracellular pathogen Salmonella enterica serovar Typhimurium requires the mgtC gene to cause disease. The mgtC transcript includes a long leader region that harbors a short proline codon-rich ORF - termed mgtP - the translation of which is predicted to favor formation of one of two alternative stem-loop structures. We now report that the mgtP proline codons are critical for expression of the mgtC coding region inside host cells, for Salmonella survival inside macrophages, and for virulence in mice. We determine that the mgtP proline codons mediate the response to proline-charged tRNAPro, the levels of which decrease under proline limitation and/or hyperosmotic stress. The host compartment harboring Salmonella appears to be limited in proline because proline auxotrophs were defective for intramacrophage survival and virulence in mice. Salmonella seems to experience hyperosmotic stress during infection because osmotically regulated genes were highly induced inside phagocytic cells. Replacing mgtP proline codons with codons specifying threonine converted the mgtC leader into a threonine-responding element. Our findings indicate that an attenuation-like mechanism governs transcription elongation into the mgtCBR coding region. Moreover, they highlight how pathogens construe host signals by the effect they have on bacterial constituents.

Original languageEnglish
Pages (from-to)3140-3145
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number8
DOIs
Publication statusPublished - 2014 Feb 25

Keywords

  • Leader mRNA
  • Transcription attenuation

ASJC Scopus subject areas

  • General

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