TRNAPro‐mediated downregulation of elongation factor P is required for mgtCBR expression during Salmonella infection. Issue 2 (2nd August 2016) - Nam, Daesil
Summary: 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 tRNA Pro, 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. Abstract : Salmonella enterica serovar Typhimurium decreases the levels of elongation factor P during course of infection, which are mediated by low levels of charged tRNA Pro . The decrease of EF‐P levels is required for selective induction of the mgtC virulence gene and Salmonella 's survival inside macrophages. Low levels of EF‐P induce ribosome stalling at the consecutive proline codons of the short open reading frame mgtP in the mgtCBR leader, promoting mgtC expression.