Elongation factor P mediates a novel post-transcriptional regulatory pathway critical for bacterial virulence

Abstract

Bacterial pathogens detect and integrate multiple environmental signals to coordinate appropriate changes in gene expression including the selective expression of virulence factors, changes to metabolism and the activation of stress response systems. Mutations that abolish the ability of the pathogen to respond to external cues are typically attenuating. Here we discuss our recent discovery of a novel post-transcriptional regulatory pathway critical for Salmonella virulence and stress resistance. The enzymes PoxA and YjeK coordinately attach a unique beta-amino acid onto a highly conserved lysine residue in the translation factor elongation factor P (EF-P). Strains in which EF-P is unmodified due to the absence of PoxA or YjeK are attenuated for virulence and display highly pleiotropic phenotypes, including hypersusceptibility to a wide range of unrelated antimicrobial compounds. Work from our laboratory and others now suggests that EF-P, previously thought to be essential, instead plays an ancillary role in translation by regulating the synthesis of a relatively limited subset of proteins. Other observations suggest that the eukaryotic homolog of EF-P, eIF5A, may illicit similar changes in the translation machinery during stress adaptation, indicating that the role of these factors in physiology may be broadly conserved.

(R)-β-Lysine-modified Elongation Factor P Functions in Translation Elongation

“…5). Taken together, these studies on di-and polypeptide synthesis indicate that EF-P is not an essential translation elongation factor and, as suggested previously from proteomic data, may instead only affect the translation of a particular subset of mRNAs (27).…”

Loss of Elongation Factor P Disrupts Bacterial Outer Membrane Integrity

“…aIF5A and eIF5A are generally considered to be essential for cellular growth, and some reports indicate that they play a role in peptide chain elongation beyond the formation of the first peptide bond, although these points remain controversial (28,34,49). While the mechanism by which EF-P, aIF5A, and eIF5A affect peptide bond synthesis at the peptidyl transferase center is likely similar, there are also considerable differences among the three proteins (61). Importantly, both aIF5A and eIF5A lack the third beta-barrel domain present in EF-P.…”

Translation Control of Swarming Proficiency in Bacillus subtilis by 5-Amino-pentanolylated Elongation Factor P

“…The rapid translation of poly-proline residues in Gammaproteobacteria is dependent on a fully modified EF-P, and absence of the modification results in aberrant phenotypes such as impaired swimming motility, growth defects, and compromised membrane integrity (6,33). In contrast, when efp is disrupted in B. subtilis, limited pleiotropy is observed, with swarming motility abolished and vegetative growth only mildly affected, calling into question the broad role of EF-P and its possible modification in B. subtilis.…”