Dual transcriptional analysis reveals adaptation of host and pathogen to intracellular survival of Pseudomonas aeruginosa associated with urinary tract infection
Fig 5
Activation of the host NF-ΚB signaling pathway is correlated with bacterial survival rather than clearance.
“Unexposed”, “exposed” but uninfected GFP negative and “invaded” GFP positive cells were infected with WT or ΔalgR PAO1 GFP-expressing bacteria and sorted 2 hpi. (A) Differential expression analysis of WT exposed and invaded cells. Differentially expressed genes (padj < 0.01) highlighted in blue; top 10 genes labeled. (B) Gene expression profiles of WT- and ΔalgR-invaded cells were compared to unexposed cells. Normalized enrichment score (NES) for gene sets significantly enriched (FDR qval<0.005) in each comparison are shown. (C) Heat map showing genes differentially expressed between WT-invaded and ΔalgR-invaded cells. Genes belonging to the TNFα via NF-κB gene set are highlighted. (D) Cells were pre-treated for 30 min with GSK 319347A or Wedelolactone before infection with WT P. aeruginosa at MOI = 10. At indicated time points, the number of intracellular bacteria was determined. (E) Cells were pre-treated with TNFα blocking monoclonal antibodies or recombinant TNFα 1 hour before infection with WT or ΔalgR P. aeruginosa, respectively, at MOI = 10. At indicated time points, the number of intracellular bacteria was determined.