title: Control of a Salmonella virulence operon by proline-charged tRNA(Pro).
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.
authors: Howard Hughes Medical Institute and Department of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale School of Medicine, New Haven, CT 06536-0812.
authors: Eun-Jin
authors: EJ
authors: Lee
authors: Jeongjoon
authors: J
authors: Choi
authors: Eduardo A
authors: EA
authors: Groisman
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D020029:Base Pairing; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D003062:Codon / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D011392:Proline / Q000235:genetics / Q000378:metabolism; D012361:RNA, Transfer, Pro / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D020121:5' Untranslated Regions; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D003062:Codon; D009838:Oligodeoxyribonucleotides; D012361:RNA, Transfer, Pro; D011392:Proline; C093586:MgtC protein, Salmonella typhimurium
keywords: leader mRNA; transcription attenuation