Brinsmade Lab

Research

Analysis of the CodY RNome reveals RsaD as a stress-responsive riboregulator of overflow metabolism

Equipped with a multitude of metabolic and biosynthetic pathways as well as secreted virulence factors, Staphylococcus aureus can adapt to essentially every environment to colonize or invade host tissues. In these locales, the activities of critical metabolic pathways and the abundance of key pathogenicity determinants can be controlled using protein- and RNA-based factors; one such regulator is the CodY protein.

We recently sought to expand knowledge of the CodY regulon to include small, non-coding regulatory RNAs (sRNAs) in addition to the well-characterized genes under CodY control. Previously, it was unknown whether CodY exerted regulatory effects on sRNAs beyond RNAIII, the effector molecule of the agr locus. We demonstrated that the trans-acting sRNA RsaD is directly repressed by CodY and serves as a novel effector of this regulator. In doing so it is responsible for the apparent positive CodY regulation of the alsSD genes by decreasing AlsSD (acetolactate synthase/decarboxylase [ASD]) enzyme activity and alsS transcript abundance. Moreover, rsaD is activated by the alternative sigma factor B (SigB) and we show that post-transcriptional regulation of ASD results in a rerouting of carbon flow at a critical metabolic node. In this manner, RsaD contributes to S. aureus death in laboratory cultures by altering the balance of acetate and acetoin excretion. Because regulated cell death is important for biofilm development, we are now focused on understanding the role of RsaD in biofilm-associated diseases. Our work and the work of others has shown that rsaD expression is controlled by a number of regulators, leading us to hypothesize that RsaD is an integrator of environmental and nutritional stresses and aligns staphylococcal physiology to the host environment.

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Brinsmade Laboratory
Department of Biology, Georgetown University

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Lab Info
Georgetown University
Department of Biology
301A Regents Hall
37th and O Streets, N.W.
Washington, DC 20057-1229

Shaun Brinsmade, PhD
Associate Professor

Office: (202) 687-6549
sb1344@georgetown.edu