Coordinated regulation of acid resistance in Escherichia coli.
BMC Syst Biol
; 11(1): 1, 2017 01 06.
Article
em En
| MEDLINE
| ID: mdl-28061857
ABSTRACT
BACKGROUND:
Enteric Escherichia coli survives the highly acidic environment of the stomach through multiple acid resistance (AR) mechanisms. The most effective system, AR2, decarboxylates externally-derived glutamate to remove cytoplasmic protons and excrete GABA. The first described system, AR1, does not require an external amino acid. Its mechanism has not been determined. The regulation of the multiple AR systems and their coordination with broader cellular metabolism has not been fully explored.RESULTS:
We utilized a combination of ChIP-Seq and gene expression analysis to experimentally map the regulatory interactions of four TFs nac, ntrC, ompR, and csiR. Our data identified all previously in vivo confirmed direct interactions and revealed several others previously inferred from gene expression data. Our data demonstrate that nac and csiR directly modulate AR, and leads to a regulatory network model in which all four TFs participate in coordinating acid resistance, glutamate metabolism, and nitrogen metabolism. This model predicts a novel mechanism for AR1 by which the decarboxylation enzymes of AR2 are used with internally derived glutamate. This hypothesis makes several testable predictions that we confirmed experimentally.CONCLUSIONS:
Our data suggest that the regulatory network underlying AR is complex and deeply interconnected with the regulation of GABA and glutamate metabolism, nitrogen metabolism. These connections underlie and experimentally validated model of AR1 in which the decarboxylation enzymes of AR2 are used with internally derived glutamate.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Mapeamento de Interação de Proteínas
/
Escherichia coli
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
BMC Syst Biol
Ano de publicação:
2017
Tipo de documento:
Article