Elongation factor P controls translation of the mgtA gene encoding a Mg²⁺ transporter during Salmonella infection

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Ribosomes stall on consecutive proline codons during mRNA translation.
• Elongation factor P (EF-P) is crucial for resolving these stalls and ensuring protein synthesis.
• EF-P's role in bacterial pathogenesis is an area of active investigation.

Purpose of the Study:

• To investigate the role of EF-P in the translation of the mgtA gene in Salmonella enterica serovar Typhimurium.
• To determine if EF-P-mediated translational control of mgtA impacts Salmonella's virulence.
• To understand the mechanism by which EF-P influences mgtA gene expression.

Main Methods:

• Site-directed mutagenesis to alter proline codons within the mgtA gene.
• Analysis of MgtA protein expression levels under different EF-P conditions.
• Assessment of Salmonella's intramacrophage survival and mouse virulence with modified mgtA genes.

Main Results:

• EF-P specifically controls the translation of the mgtA gene, which encodes a Mg2+-transporting ATPase.
• Mutations at proline codons 550 and 551 of mgtA abolished EF-P-dependent translational control.
• The modified mgtA gene, independent of EF-P control, enhanced Salmonella's intramacrophage survival and virulence in mice.

Conclusions:

• EF-P-mediated translational regulation of the mgtA gene is essential for Salmonella pathogenesis.
• The proline codons within mgtA are critical for EF-P's regulatory function.
• Targeting EF-P-mgtA interactions could represent a novel therapeutic strategy against Salmonella infections.