RNAseq transcriptome analysis of Streptococcus pneumoniae 23F treated with PBT2 and zinc

Streptococcus pneumoniae is the primary cause of community-acquired bacterial pneumonia with rates of penicillin and multi-drug resistance exceeding 80% and 40%, respectively. The innate immune response uses various chemical insults to control infection, including metal stress mediated by localized changes in zinc abundance. Here, we characterized the impact of S. pneumoniae zinc intoxication revealing disruptions in central carbon metabolism, lipid biogenesis and peptidoglycan biosynthesis. To dysregulate zinc homeostasis in the wild-type strain, we investigated the safe-for-human use ionophore PBT2. PBT2 rendered wild-type S. pneumoniae strains sensitive to a range of antibiotics. Overall design: For each species of S. pneumoniae 23F, 2 sample conditions in triplicate were analyzed. Sample conditions included: 1) bacterial treatment with cation-adjusted Muller Hinton broth (CA-MHB; reference sample); or 2) CA-MHB + 32 µM PBT2 + 8 µM ZnSO4.