OxyR Is a Convergent Target for Mutations Acquired during Adaptation to Oxidative Stress-Prone Metabolic States.
Mol Biol Evol
; 37(3): 660-667, 2020 03 01.
Article
em En
| MEDLINE
| ID: mdl-31651953
ABSTRACT
Oxidative stress is concomitant with aerobic metabolism. Thus, bacterial genomes encode elaborate mechanisms to achieve redox homeostasis. Here we report that the peroxide-sensing transcription factor, oxyR, is a common mutational target using bacterial species belonging to two genera, Escherichia coli and Vibrio natriegens, in separate growth conditions implemented during laboratory evolution. The mutations clustered in the redox active site, dimer interface, and flexible redox loop of the protein. These mutations favor the oxidized conformation of OxyR that results in constitutive expression of the genes it regulates. Independent component analysis of the transcriptome revealed that the constitutive activity of OxyR reduces DNA damage from reactive oxygen species, as inferred from the activity of the SOS response regulator LexA. This adaptation to peroxide stress came at a cost of lower growth, as revealed by calculations of proteome allocation using genome-scale models of metabolism and macromolecular expression. Further, identification of similar sequence changes in natural isolates of E. coli indicates that adaptation to oxidative stress through genetic changes in oxyR can be a common occurrence.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Fatores de Transcrição
/
Vibrio
/
Proteínas de Escherichia coli
/
Escherichia coli
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Mol Biol Evol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá