Steady-state hydrogen peroxide induces glycolysis in Staphylococcus aureus and Pseudomonas aeruginosa.
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 H2O2 by bacterial catalase, only steady-state but not one-dose treatment with H2O2 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 H2O2, which revealed profound transcriptional changes, including the induced expression of glycolytic genes in both bacteria. Our results revealed that the inactivation of GAPDH by H2O2 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 H2O2-stalled glycolysis in S. aureus and P. aeruginosa, respectively. Both GapR and HexR may directly sense oxidative stresses, such as menadione.
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.
Xin
X
Deng
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.
Haihua
H
Liang
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA.
Olesya A
OA
Ulanovskaya
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.
Quanjiang
Q
Ji
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.
Tianhong
T
Zhou
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.
Fei
F
Sun
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.
Zhike
Z
Lu
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.
Alan L
AL
Hutchison
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Pudong Zhangjiang Hi-Tech Park, Shanghai, China.
Lefu
L
Lan
Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, USA.
Min
M
Wu
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA.
Benjamin F
BF
Cravatt
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA chuanhe@uchicago.edu.
Chuan
C
He
D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005942:Gluconates / Q000378:metabolism; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D059467:Transcriptome
D005942:Gluconates; D016877:Oxidants; D012329:RNA, Bacterial; C081217:2-keto-3-deoxy-6-phosphogluconate; D006861:Hydrogen Peroxide; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)