Journal article
The iron-regulated small regulatory RNA IsrR modulates expression of genes utilized for dioxygen metabolism and heme synthesis in Staphylococcus aureus
mBio, Vol.16(11), e01415-25
11/2025
DOI: 10.1128/mbio.01415-25
PMCID: PMC12607789
PMID: 41042061
Abstract
Bacterial regulatory RNAs (sRNAs) are commonly short non-coding RNAs that function as pleiotropic regulators by post-transcriptionally impacting mRNA stability and/or translation. They play significant roles in bacterial physiology and are typically expressed in response to specific environmental stimuli such as nutrient limitation. The bacterial pathogen Staphylococcus aureus faces decreased access to essential metal ions, including iron, in the mammalian host via a process called nutritional immunity. In response to host-mediated iron limitation, S. aureus expresses the sRNA IsrR, which coordinates an iron-sparing response by downregulating the expression of mRNAs coding for iron-requiring proteins or processes. Herein, we utilized MS2-Affinity Purification coupled with RNA Sequencing (MAPS) to reveal the in vivo IsrR interaction network. Analysis of co-purified RNAs revealed previously unpredicted putative IsrR targets coding for proteins associated with iron-requiring processes. We validated that IsrR directly interacts with nine targets in vitro. We demonstrate physiological roles for IsrR in mediating heme biosynthesis, aerobic respiration, and the detoxification of oxygen radicals. These activities are critical for pathogenesis, and this study establishes how S. aureus leverages these processes to adapt to iron scarcity, which is commonly encountered in the mammalian host.
Details
- Title: Subtitle
- The iron-regulated small regulatory RNA IsrR modulates expression of genes utilized for dioxygen metabolism and heme synthesis in Staphylococcus aureus
- Creators
- Gustavo Rios-Delgado - Rutgers, The State University of New JerseyRiley Mcfarlane - University of IowaVincent Zheng - Rutgers, The State University of New JerseyJisun Kim - Rutgers, The State University of New JerseyDane Parker - Rutgers, The State University of New JerseyThomas Kehl-Fie - University of IowaDavid Lalaouna - Architecture et Réactivité de l'arNJeffrey Boyd - Rutgers, The State University of New Jersey
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.16(11), e01415-25
- DOI
- 10.1128/mbio.01415-25
- PMID
- 41042061
- PMCID
- PMC12607789
- NLM abbreviation
- mBio
- ISSN
- 2161-2129
- eISSN
- 2150-7511
- Publisher
- American Society for Microbiology
- Grant note
- National Science Foundation: 1R01AI139100 NIAID: 1750624 National Science Foundation: NE-2248 USDA MRF project: ANR-20-CE12-0021, ITI 2021-2028 Agence Nationale de la RechercheCNRSInserm: ANR-10-IDEX-0002, ANR-20-SFRI-0012, ANR-17-EURE-0023, R01 AI155611 IdEx UnistraThomas Jefferson Fund, a program of the FACE Foundation
The Boyd lab was supported by NIAID 1R01AI139100, National Science Foundation award 1750624, and USDA MRF project NE-2248 to J.M.B. D.L. was supported by the Agence Nationale de la Recherche (ANR-20-CE12-0021) and the Interdisciplinary Thematic Institute IMCBio+, as part of the ITI 2021-2028 program of the University of Strasbourg, CNRS and Inserm, IdEx Unistra (ANR-10-IDEX-0002), SFRI-STRAT'US (ANR-20-SFRI-0012), and EUR IMCBio (ANR-17-EURE-0023) under the framework of the French Investments of the France 2030 Program. T.K.-F. was supported by R01 AI155611. D.L. and T.K.-F. were supported by the Thomas Jefferson Fund, a program of the FACE Foundation launched in collaboration with the French Embassy.
- Language
- English
- Electronic publication date
- 10/03/2025
- Date published
- 11/2025
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984969109502771
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