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Publications

Journal Article Ppublish

PubMed: 42755362 DOI: 10.1093/nar/gkag894

A Zur-dependent regulatory RNA involved in maintaining zinc homeostasis in Staphylococcus aureus.

Nucleic Acids Res 54(17)

Authors: Mathilde Charbonnier, Hugo Racine, Samuel Probst-Lotze, Jana N Radin, Gustavo Rios-Delgado, Liangyu Lyu, Hannah M Laster, Maximilian P Kohl, RafaƂ Mazgaj, Marion Blum, Virginie Marchand, Johana Chicher, Pascale Romby, Stefano Marzi, Isabelle Caldelari, Jai J Tree, Kevin J Waldron, Jeffrey M Boyd, Julien Y Dutheil, Thomas E Kehl-Fie, David Lalaouna

Affiliations

  • UniversitĂ© de Strasbourg, CNRS, Architecture et RĂ©activitĂ© de l'ARN, UPR9002, F-67000 Strasbourg, France.
  • Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.
  • Department of Biochemistry and Microbiology, Rutgers, the State University of New Jersey, New Brunswick, NJ 08901, United States.
  • Laboratory of Metalloprotein Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw 02-106, Poland.
  • IMoPA UMR7365 CNRS-UL, BioPole UniversitĂ© de Lorraine, VandƓuvre-lĂšs-Nancy 54505, France.
  • Plateforme de ProtĂ©omique Strasbourg-Esplanade, CNRS UAR1589, F-67000 Strasbourg, France.
  • School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
  • Department of Theoretical Biology, Max Planck Institute of Evolutionary Biology, Plön D-24306, Germany.

Abstract

Small regulatory RNAs (sRNAs) are key drivers of bacterial adaptation to environmental fluctuations, including iron and manganese restriction imposed by the host. This study explored the repertoire of sRNAs produced by the human pathogen Staphylococcus aureus in response to metal limitation. Two sRNAs were identified, S1077 and ZinS, that were regulated by zinc (Zn) availability. Further investigations revealed that, similar to the cnt operon from which it derives, S1077 synthesis is controlled by the transcription factors Zur and Fur. In contrast, zinS transcription is solely repressed by Zur. RNA affinity purification identified several ZinS-associated mRNAs encoding Zn-dependent enzymes, including the alcohol dehydrogenase Adh, whose synthesis is negatively regulated by ZinS. Loss of ZinS does not alter staphylococcal metal accumulation, suggesting a role in a Zn-sparing response. Remarkably, zinS also encodes a small peptide, ZinP. Genomic analysis shows that the regulatory portion of zinS emerged from the 3' untranslated region of zinP and is conserved in S. aureus and closely related species, whereas zinP is also found in phylogenetically distant organisms. Our findings demonstrate that sRNAs facilitate bacterial adaptation to Zn limitation, and that genetic exchange and subsequent neofunctionalization have enabled S. aureus to adapt to metal-restricted environments.

MeSH

Staphylococcus, Homeostasis, Nucleic Acids, Staphylococcus Aureus