Thermal and Nutritional Regulation of Ribosome Hibernation in Staphylococcus aureus

Author:

Basu Arnab1,Shields Kathryn E.1,Eickhoff Christopher S.2,Hoft Daniel F.2,Yap Mee-Ngan F.1ORCID

Affiliation:

1. Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

2. Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, USA

Abstract

The dimerization of 70S ribosomes (100S complex) plays an important role in translational regulation and infectivity of the major human pathogen Staphylococcus aureus . Although the dimerizing factor HPF has been characterized biochemically, the pathways that regulate 100S ribosome abundance remain elusive. We identified a metabolite- and nutrient-sensing transcription factor, CodY, that serves both as an activator and a repressor of hpf expression in nutrient- and temperature-dependent manners. Furthermore, CodY-mediated activation of hpf masks a secondary hpf transcript derived from a general stress response SigB promoter. CodY and SigB regulate a repertoire of virulence genes. The unexpected link between ribosome homeostasis and the two master virulence regulators provides new opportunities for alternative druggable sites.

Funder

HHS | National Institutes of Health

Pew Charitable Trusts

Edward Mallinckrodt, Jr. Foundation

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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