Elongation factor P restricts Salmonella's growth by controlling translation of a Mg2+transporter gene during infection.
When a ribosome translates mRNA sequences, the ribosome often stalls at certain codons because it is hard to translate. Consecutive proline codons are such examples that induce ribosome stalling and elongation factor P (EF-P) is required for the stalled ribosome to continue translation at those consecutive proline codons. We found that EF-P is required for translation of the mgtB gene encoding a Mg2+transporter in the mgtCBR virulence operon from the intracellular pathogen Salmonella enterica serovar Typhimurium. Salmonella lacking EF-P decreases MgtB protein levels in a manner dependent on consecutive proline codons located in the mgtB coding region despite increasing transcription of the mgtCBR operon via the mgtP open reading frame in the leader RNA, resulting in an altered ratio between MgtC and MgtB proteins within the operon. Substitution of the consecutive proline codons to alanine codons eliminates EF-P-mediated control of the mgtB gene during infection and thus contributes to Salmonella's survival inside macrophages where Salmonella experiences low levels of EF-P. This suggests that this pathogen utilizes a strategy to coordinate expression of virulence genes by an evolutionarily conserved translation factor.
Department of Genetic Engineering and Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, South Korea.
Eunna
E
Choi
Department of Genetic Engineering and Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, South Korea.
Soomin
S
Choi
Division of Microbiology, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 16419, South Korea.
Daesil
D
Nam
Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, South Korea.
Shinae
S
Park
Department of Genetic Engineering and Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, South Korea.
Yoontak
Y
Han
Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, South Korea.
Jung-Shin
JS
Lee
Department of Genetic Engineering and Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, South Korea.
Eun-Jin
EJ
Lee
D000251:Adenosine Triphosphatases / Q000096:biosynthesis*; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis*; D027682:Cation Transport Proteins / Q000096:biosynthesis*; D002460:Cell Line; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D008264:Macrophages / Q000382:microbiology; D008809:Mice, Inbred C3H; D050296:Microbial Viability; D010445:Peptide Elongation Factors / Q000172:deficiency / Q000378:metabolism*; D014176:Protein Biosynthesis; D012481:Salmonella Infections, Animal / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000254:growth & development*; D014774:Virulence
D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D010445:Peptide Elongation Factors; C020746:factor EF-P; D000251:Adenosine Triphosphatases; C083836:MgtB protein, Salmonella typhimurium