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 tRNA(Pro), 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Lee EJ,Choi J,Groisman EAdoi
10.1073/pnas.1316209111subject
Has Abstractpub_date
2014-02-25 00:00:00pages
3140-5issue
8eissn
0027-8424issn
1091-6490pii
1316209111journal_volume
111pub_type
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