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Steady-state hydrogen peroxide induces glycolysis via metabolic reroute in P. aeruginosa and S. aureus

ABSTRACT: GAPDHs from human pathogens S. aureus and P. aeruginosa can be readily inhibited by ROS-mediated direct oxidation of their catalytic active cysteines. Because of the rapid degradation of H2O2 by bacterial catalase, only steady-state but not one-dose treatment of H2O2 induces rapid metabolic reroute from glycolysis to pentose phosphate pathway (PPP). We conducted RNA-seq analyses to globally profile the bacterial transcriptomes in response to a steady level of H2O2, which reveals profound transcriptional changes including the induced expression of glycolytic genes in both bacteria. Our results revealed that the inactivation of GAPDH by H2O2 induces a metabolic reroute from glycolysis to PPP; the elevated levels of fructose 1,6-biphosphate (FBP) and 2-keto-3-deoxy-6-phosphogluconate (KDPG) lead to dissociation of their corresponding glycolytic repressors (GapR and HexR, respectively) from their cognate promoters, thus resulting in derepression of the glycolytic genes to overcome H2O2-stalled glycolysis in S. aureus and P. aeruginosa, respectively. Given that H2O2 can be produced constitutively by the host immune response, exposure to the steady-state stress of H2O2 recapitulates more accurately bacterial responses to host immune system in vivo.

ORGANISM(S): Staphylococcus aureus subsp. aureus str. Newman Pseudomonas aeruginosa MPAO1/P1

PROVIDER: GSE55528 | GEO | 2014/05/08

SECONDARY ACCESSION(S): PRJNA239877

REPOSITORIES: GEO

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Steady-state hydrogen peroxide induces glycolysis via metabolic reroute in P. aeruginosa and S. aureus

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