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

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 β-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

Parental nucleosome segregation and the inheritance of cellular identity

Gene expression programmes conferring cellular identity are achieved through the organization of chromatin structures that either facilitate or impede transcription. Among the key determinants of chromatin organization are the histone modifications that correlate with a given transcriptional status and chromatin state. Until recently, the details for the segregation of nucleosomes on DNA replication and their implications in re-establishing heritable chromatin domains remained unclear. Here, we review recent findings detailing the local segregation of parental nucleosomes and highlight important advances as to how histone methyltransferases associated with the establishment of repressive chromatin domains facilitate epigenetic inheritance. Maintenance of cell-type identity requires the faithful inheritance of chromatin states through cell division, despite the challenges posed by the disruptive passage of the DNA replication fork and the dilution of nucleosome components in complex with the daughter DNA strands. In this Review, Escobar, Loyola and Reinberg discuss how methodological advances are providing unprecedented mechanistic insights into the segregation of parental nucleosomes, how these mechanisms maintain gene expression programmes and how non-faithful nucleosome segregation is linked to differentiation and disease