Steady-State Hydrogen Peroxide Induces Glycolysis in Staphylococcus aureus and Pseudomonas aeruginosa

Abstract

ABSTRACT Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from human pathogens Staphylococcus aureus and Pseudomonas aeruginosa can be readily inhibited by reactive oxygen species (ROS)-mediated direct oxidation of their catalytic active cysteines. Because of the rapid degradation of H 2 O 2 by bacterial catalase, only steady-state but not one-dose treatment with H 2 O 2 rapidly induces glycolysis and the pentose phosphate pathway (PPP). We conducted transcriptome sequencing (RNA-seq) analyses to globally profile the bacterial transcriptomes in response to a steady level of H 2 O 2 , which revealed profound transcriptional changes, including the induced expression of glycolytic genes in both bacteria. Our results revealed that the inactivation of GAPDH by H 2 O 2 induces metabolic levels of glycolysis and the 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 H 2 O 2 -stalled glycolysis in S. aureus and P. aeruginosa , respectively. Both GapR and HexR may directly sense oxidative stresses, such as menadione.