BioProject

Staphylococcus aureus is a human commensal bacterium and opportunistic pathogen. More...

Staphylococcus aureus is a human commensal bacterium and opportunistic pathogen. Chronicity of S. aureus infection has been linked to bacterial survival within host cells including macrophages. Bacteria recovered from the intracellular milieu often form small colony variants (SCV) which are growing slowly, show reduced virulence factor production and are more resistant to antibiotics. Branched chain amino acids (BCAA) are an important class of nutrients for S. aureus. We therefore tested if components of BCAA biosynthesis or transport would alter the outcome of macrophage infection. We found that S. aureus mutants in the BCAA transporter BrnQ1 survived experimental infection of primary human macrophages for the complete duration of the 28 day experiments. Since phenotypic differences between brnQ1 mutants and wild-type bacteria occurred around 10 h p.i., we performed dual RNA-seq by which we determined the transcriptomes of both, pathogen and macrophage host, simultaneously. Our data indicate that at that time transcriptomic changes exclusively are governed by the internalized pathogen. The differential analysis of S. aureus WT and its isogenic brnQ1 mutant surprisingly demonstrated a dysregulation of iron-dependently regulated genes. Overall design: S. aureus JE2 wild-type or its isogenic brnQ1 mutant were either used to infect human macrophages or were grown in RPMI1640. RNA of both, pathogen and host cells were isolated together (dual RNA-Seq of infected macrophages) or was isolated from planktonic bacteria (RPMI1640). Less...