A Zur-dependent regulatory RNA involved in maintaining zinc homeostasis in Staphylococcus aureus
Year: 2026
Type: article
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.
Source: Nucleic Acids Research
DOI: 10.1093/nar/gkag894
Authors: Mathilde Charbonnier, Hugo Racine, Samuel Probst-Lotze, Jana N Radin, Gustavo Rios-Delgado, Liangyu Lyu, Hannah M Laster, Maximilian P Kohl, Rafał 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
Institutions: Centre National de la Recherche Scientifique, Architecture et Réactivité de l'arN, Université de Strasbourg, University of Iowa, Rutgers, The State University of New Jersey, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Polish Academy of Sciences, Ingénierie Moléculaire, Cellulaire et Physiopathologie, Université de Lorraine, Institut de Biologie Moléculaire et Cellulaire, UNSW Sydney, Max Planck Institute for Evolutionary Biology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,992
Funders: National Science Foundation, U.S. Department of Agriculture, FACE Foundation, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Centre National de la Recherche Scientifique, National Institutes of Health, Medical Research Council, Australian Research Council, National Health and Medical Research Council, National Institute of Allergy and Infectious Diseases
Awards: CAREER: Iron-sulfur cluster assembly in Bacillus subtilis, G1190173965, G164444715, G1800105685, Par-delà les frontières, l'Université de Strasbourg, G2255650664, G2659019386, G2694206344, Façonner les talents en formation et en recherche à l'Université de Strasbourg, G2980570810, G3357951378, G3730343, G399734812, G4381811279, Integrative Molecular and Cellular Biology, Decoding regulatory RNA function in bacteria, G471331628, G4779185514, G4844819464, G5296751580, G6136357505, G6276897512, G6389594462, G6405104111, An integrated investigation of regulatory RNAs and their interacting proteins in bacteria models, G6803667113, G6888366887, G7080048889, G7240651115, Staphylococcus aureus sRNA-mediated adaptation to metal-based host defense strategies, Calprotectin and Antibiotic Activities at the Infection Interface, Enhancing antisense RNA antibiotics using aptamers that trigger RNA decay, Leveraging host-imposed metal starvation to elucidate the molecular and environmental factors that dictate metal utilization by the iron/manganese superoxide dismutase superfamily
OpenAlex ID: W7213542857