Control of a Salmonella virulence operon by proline-charged tRNA(Pro).
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.
['Lee|Eun-Jin|EJ|', 'Choi|Jeongjoon|J|', 'Groisman|Eduardo A|EA|']
D020121:5' Untranslated Regions D000595:Amino Acid Sequence D000818:Animals D001426:Bacterial Proteins D020029:Base Pairing D001483:Base Sequence D027682:Cation Transport Proteins D003062:Codon D015964:Gene Expression Regulation, Bacterial D054884:Host-Pathogen Interactions D051379:Mice D008969:Molecular Sequence Data D009838:Oligodeoxyribonucleotides D016366:Open Reading Frames D011392:Proline D012361:RNA, Transfer, Pro D060888:Real-Time Polymerase Chain Reaction D012486:Salmonella typhimurium D014774:Virulence
leader mRNA transcription attenuation