Affordable Access

deepdyve-link
Publisher Website

Analysis of the CodY RNome reveals RsaD as a stress-responsive riboregulator of overflow metabolism in Staphylococcus aureus.

Authors
  • Augagneur, Yoann1
  • King, Alyssa N2
  • Germain-Amiot, Noëlla1
  • Sassi, Mohamed1
  • Fitzgerald, John W2
  • Sahukhal, Gyan S3
  • Elasri, Mohamed O3
  • Felden, Brice1
  • Brinsmade, Shaun R2
  • 1 INSERM U1230 Biochimie Pharmaceutique, Université de Rennes I, Rennes, France. , (France)
  • 2 Department of Biology, Georgetown University, Washington, DC, USA.
  • 3 Center of Molecular and Cellular Biosciences, The University of Southern Mississippi, Hattiesburg, MS, USA.
Type
Published Article
Journal
Molecular Microbiology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Feb 01, 2020
Volume
113
Issue
2
Pages
309–325
Identifiers
DOI: 10.1111/mmi.14418
PMID: 31696578
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In Staphylococcus aureus, the transcription factor CodY modulates the expression of hundreds of genes, including most virulence factors, in response to the availability of key nutrients like GTP and branched-chain amino acids. Despite numerous studies examining how CodY controls gene expression directly or indirectly, virtually nothing is known about the extent to which CodY exerts its effect through small regulatory RNAs (sRNAs). Herein, we report the first set of sRNAs under the control of CodY. We reveal that staphylococcal sRNA RsaD is overexpressed >20-fold in a CodY-deficient strain in three S. aureus clinical isolates and in S. epidermidis. We validated the CodY-dependent regulation of rsaD and demonstrated that CodY directly represses rsaD expression by binding the promoter. Using a combination of molecular techniques, we show that RsaD posttranscriptionally regulates alsS (acetolactate synthase) mRNA and enzyme levels. We further show that RsaD redirects carbon overflow metabolism, contributing to stationary phase cell death during exposure to weak acid stress. Taken together, our data delineate a role for CodY in controlling sRNA expression in a major human pathogen and indicate that RsaD may integrate nutrient depletion and other signals to mount a response to physiological stress experienced by S. aureus in diverse environments. © 2019 John Wiley & Sons Ltd.

Report this publication

Statistics

Seen <100 times