title: tRNAPro-mediated downregulation of elongation factor P is required for mgtCBR expression during Salmonella infection.
abstract: Bacterial ribosome requires elongation factor P to translate fragments harbouring consecutive proline codons. Given the abundance of ORFs with potential EF-P regulated sites, EF-P was assumed to be constitutively expressed. Here, we report that the intracellular pathogen Salmonella enterica serovar Typhimurium decreases efp mRNA levels during course of infection. We determined that the decrease in efp mRNA is triggered by low levels of charged tRNAPro, a condition that Salmonella experiences when inside a macrophage phagosome. Surprisingly, downregulation of EF-P selectively promotes expression of the virulence mgtC gene and contributes to Salmonella's ability to survive inside macrophages. The decrease in EF-P levels induces ribosome stalling at the consecutive proline codons of the mgtP open reading frame in the mgtCBR leader RNA, and thus allows formation of a stem-loop structure promoting transcription of the mgtC gene. The substitution of proline codons in the mgtP gene eliminates EF-P-mediated mgtC expression and thus Salmonella's survival inside macrophages. Our findings indicate that Salmonella benefits virulence genes by decreasing EF-P levels and inducing the stringent response inside host.
authors.affiliation: Division of Microbiology, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea.
authors.forename: Daesil
authors.initials: D
authors.lastname: Nam
authors.affiliation: Department of Genetic Engineering and Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 17104, South Korea.
authors.forename: Eunna
authors.initials: E
authors.lastname: Choi
authors.affiliation: Division of Microbiology, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea.
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Genetic Engineering and Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 17104, South Korea. eunjinlee@khu.ac.kr.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D015964:Gene Expression Regulation, Bacterial; D020868:Gene Silencing; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D016366:Open Reading Frames; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D012361:RNA, Transfer, Pro / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D012480:Salmonella Infections / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D010445:Peptide Elongation Factors; D012361:RNA, Transfer, Pro; D037521:Virulence Factors; C020746:factor EF-P