Global translation variations in host cells upon attack of lytic and sublytic Staphylococcus aureus α-haemolysin

Biochem J. 2015 Nov 15;472(1):83-95. doi: 10.1042/BJ20150284. Epub 2015 Sep 14.

Abstract

Genome-wide analyses of translation can provide major contributions in our understanding of the complex interplay between virulent factors and host cells. So far, the activation of host translational control mechanisms by bacterial toxins, owing to specific recruitment of mRNAs, RNA-binding proteins (RBPs) and ncRNAs (non-coding RNAs), are far from being understood. In the present study, we characterize for the first time the changes experienced by the translational control system of host cells in response to the well-known Staphylococcus aureus α-haemolysin (AHL) under both sublytic and lytic conditions. By comparing variations occurring in the cellular transcriptome and translatome, we give evidence that global gene expression is primarily rewired at the translational level, with the contribution of the RBP ELAVL1 (HuR) in the sublytic response. These results reveal the importance of translational control during host-pathogen interaction, opening new approaches for AHL-induced diseases.

Keywords: HuR; RNA-binding protein; bacterial toxins; polysomal profiling; pore-forming toxins; transcriptome; translational control; translatome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism
  • Bacterial Toxins / pharmacology*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • ELAV-Like Protein 1 / genetics
  • ELAV-Like Protein 1 / metabolism
  • Gene Expression Profiling / methods
  • Genetic Variation / drug effects*
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / metabolism
  • Hemolysin Proteins / pharmacology*
  • Humans
  • Immunoblotting
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Protein Biosynthesis / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptome / genetics*

Substances

  • Bacterial Toxins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • Hemolysin Proteins
  • staphylococcal alpha-toxin