A Repeat-Associated Small RNA Controls the Major Virulence Factors of Helicobacter pylori.
Mol Cell
; 80(2): 210-226.e7, 2020 10 15.
Article
em En
| MEDLINE
| ID: mdl-33002424
Many bacterial pathogens regulate their virulence genes via phase variation, whereby length-variable simple sequence repeats control the transcription or coding potential of those genes. Here, we have exploited this relationship between DNA structure and physiological function to discover a globally acting small RNA (sRNA) regulator of virulence in the gastric pathogen Helicobacter pylori. Our study reports the first sRNA whose expression is affected by a variable thymine (T) stretch in its promoter. We show the sRNA post-transcriptionally represses multiple major pathogenicity factors of H. pylori, including CagA and VacA, by base pairing to their mRNAs. We further demonstrate transcription of the sRNA is regulated by the nickel-responsive transcriptional regulator NikR (thus named NikS for nickel-regulated sRNA), thereby linking virulence factor regulation to nickel concentrations. Using in-vitro infection experiments, we demonstrate NikS affects host cell internalization and epithelial barrier disruption. Together, our results show NikS is a phase-variable, post-transcriptional global regulator of virulence properties in H. pylori.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Bacteriano
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Sequências Repetitivas de Ácido Nucleico
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Helicobacter pylori
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Fatores de Virulência
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article