Analysis of the CodY RNome reveals RsaD as a stress‐responsive riboregulator of overflow metabolism in Staphylococcus aureus. Issue 2 (16th December 2019)

• Record Type: Journal Article
• Authors: Augagneur, Yoann; King, Alyssa N.; Germain‐Amiot, Noëlla; Sassi, Mohamed; Fitzgerald, John W.; Sahukhal, Gyan S.; Elasri, Mohamed O.; Felden, Brice; Brinsmade, Shaun R.
• Is Part Of: Molecular microbiology. Volume 113:Issue 2(2019)
• Page Start: 309
• Page End: 325
• Publication Date: 2019-12-16
• Subjects: Gram‐positive -- physiology -- posttranscriptional -- regulation -- sRNA -- staphylococci; Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14418
• Languages: English
• ISSNs: 0950-382X

Abstract

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. Abstract : Understanding the mechanisms by which Staphylococcus aureus adapts to the constraints of the diverse host niches in which it inhabits is critical to developing novel treatments. The current study examines the role of global regulator CodY in regulating small RNAs (sRNAs), and shows that one, RsaD, is a trans ‐acting sRNA that affects carbon overflow metabolism. In doing so, RsaD fine tunes acetate and acetoin production to regulate cell death during the stationary phase.