Gre factors help Salmonella adapt to oxidative stress by improving transcription elongation and fidelity of metabolic genes

Detoxification, scavenging, and repair systems embody the archetypical antioxidant defenses of prokaryotic and eukaryotic cells. Metabolic rewiring also aids with the adaptation of bacteria to oxidative stress. Evolutionarily diverse bacteria combat the toxicity of reactive oxygen species (ROS) by a...

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Bibliographic Details
Published in:PLoS biology 2023-04, Vol.21 (4), p.e3002051-e3002051
Main Authors: Kant, Sashi, Till, James Karl A, Liu, Lin, Margolis, Alyssa, Uppalapati, Siva, Kim, Ju-Sim, Vazquez-Torres, Andres
Format: Article
Language:English
Subjects:
Accuracy
Adaptation
Aerobic respiration
Amino acids
Antimicrobial agents
Antioxidants
Bacteria
Biology and Life Sciences
Cytochrome
Cytochrome bd
Cytochromes
Cytotoxicity
Dehydrogenases
Detoxification
DksA protein
DNA-directed RNA polymerase
Elongation
Fidelity
Gene expression
Genes
Glucose
Glucose - metabolism
Glycolysis
Medicine and Health Sciences
Metabolic pathways
Metabolism
NAD(P)H oxidase
NADPH Oxidases - metabolism
Overflow
Oxidase
Oxidation resistance
Oxidation-Reduction
Oxidative stress
Oxidative Stress - genetics
Pathogenesis
Physical Sciences
Proteins
Reactive oxygen species
Respiration
RNA polymerase
Salmonella
Salmonella - genetics
Scavenging
Stringent response
Toxicity
Transcription elongation
Transcription initiation
Virulence
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Summary:Detoxification, scavenging, and repair systems embody the archetypical antioxidant defenses of prokaryotic and eukaryotic cells. Metabolic rewiring also aids with the adaptation of bacteria to oxidative stress. Evolutionarily diverse bacteria combat the toxicity of reactive oxygen species (ROS) by actively engaging the stringent response, a stress program that controls many metabolic pathways at the level of transcription initiation via guanosine tetraphosphate and the α-helical DksA protein. Studies herein with Salmonella demonstrate that the interactions of structurally related, but functionally unique, α-helical Gre factors with the secondary channel of RNA polymerase elicit the expression of metabolic signatures that are associated with resistance to oxidative killing. Gre proteins both improve transcriptional fidelity of metabolic genes and resolve pauses in ternary elongation complexes of Embden-Meyerhof-Parnas (EMP) glycolysis and aerobic respiration genes. The Gre-directed utilization of glucose in overflow and aerobic metabolism satisfies the energetic and redox demands of Salmonella, while preventing the occurrence of amino acid bradytrophies. The resolution of transcriptional pauses in EMP glycolysis and aerobic respiration genes by Gre factors safeguards Salmonella from the cytotoxicity of phagocyte NADPH oxidase in the innate host response. In particular, the activation of cytochrome bd protects Salmonella from phagocyte NADPH oxidase-dependent killing by promoting glucose utilization, redox balancing, and energy production. Control of transcription fidelity and elongation by Gre factors represent important points in the regulation of metabolic programs supporting bacterial pathogenesis.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3002051