Academic Journal
Discovery of Staphylococcus aureus small RNAs highly expressed during human chronic infection.
| Τίτλος: | Discovery of Staphylococcus aureus small RNAs highly expressed during human chronic infection. |
|---|---|
| Συγγραφείς: | Briaud P; School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA.; Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, Georgia, USA., Schumacher J; School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA.; Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, Georgia, USA., Whiteley M; School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA.; Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, Georgia, USA.; Emory-Children's Cystic Fibrosis Center, Atlanta, Georgia, USA. |
| Πηγή: | MBio [mBio] 2026 Sep 09; Vol. 17 (9), pp. e0063726. Date of Electronic Publication: 2026 Aug 07. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, D.C. : American Society for Microbiology |
| Ιατρικοί όροι (MeSH): | Staphylococcus aureus*/genetics , Staphylococcus aureus*/metabolism , Staphylococcal Infections*/microbiology , RNA, Bacterial*/genetics , Persistent Infection*/microbiology , RNA, Small Untranslated*/genetics , Gene Expression Regulation, Bacterial*, Zinc/metabolism ; Cystic Fibrosis/microbiology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Humans ; Gene Expression Profiling ; Transcriptome |
| Περίληψη: | Understanding bacterial gene expression in natural environments remains challenging because most regulatory networks are inferred from in vitro models that poorly capture in situ environmental conditions. Here, we present NEMO (network transcriptomics of microbes in native environments), a generalizable pangenome-based metatranscriptomic framework for extracting microbial transcriptional programs from metatranscriptomes generated from natural samples. We applied NEMO to Staphylococcus aureus metatranscriptomes from human chronic wounds and cystic fibrosis sputum, revealing infection-associated transcriptional states that diverged markedly from in vitro growth conditions. Notably, small RNAs (sRNAs) were key drivers of the transcriptional divergence between human infection-derived and in vitro transcriptomes. Among these, we identify rsaX20 as a previously uncharacterized, zinc-responsive sRNA that also encodes a small peptide. Meta-analysis of more than 2,000 publicly available S. aureus RNA-seq data sets showed that rsaX20 is induced under zinc limitation and host-associated stress and is co-regulated with known metal-responsive sRNAs. Genetic, transcriptomic, and proteomic analyses demonstrated that rsaX20 is repressed by the zinc regulator Zur and functions as a dual-purpose sRNA/small open reading frame, with the RNA and peptide exerting distinct, sometimes opposing, effects on target proteins. Together, these findings establish NEMO as a broadly applicable framework for interrogating microbial gene regulation directly from native metatranscriptomes and identify rsaX20 as a key regulator of zinc homeostasis during chronic human S. aureus infection. Importance: Most knowledge of bacterial gene regulation comes from laboratory cultures, yet pathogens behave very differently inside the human body. We introduce NEMO, a pangenome-based framework that enables direct analysis of microbial gene expression from natural infection samples. Applying NEMO to human Staphylococcus aureus infections revealed transcriptional programs that differ substantially from standard in vitro models and highlighted small regulatory RNAs as major drivers of this divergence. Using this approach, we discovered rsaX20, a previously uncharacterized zinc-responsive regulatory RNA that also encodes a small peptide with distinct biological functions. These findings demonstrate the power of studying microbes in their native environments and uncover a key regulator of zinc homeostasis during chronic human infection. |
| Competing Interests: | The authors declare no conflict of interest. |
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| Grant Information: | R21 AI190856 United States AI NIAID NIH HHS; R21AI190856 National Institute of Allergy and Infectious Diseases |
| Contributed Indexing: | Keywords: Staphylococcus aureus; chronic infection; chronic wound infection; cystic fibrosis; in vivo gene expression; metatranscriptomic; pangenome; small regulatory RNA (sRNA); zinc; zinc homeostasis |
| Substance Nomenclature: | 0 (RNA, Bacterial) J41CSQ7QDS (Zinc) 0 (Bacterial Proteins) 0 (RNA, Small Untranslated) |
| Entry Date(s): | Date Created: 20260807 Date Completed: 20260909 Latest Revision: 20260912 |
| Update Code: | 20260912 |
| PubMed Central ID: | PMC13556194 |
| DOI: | 10.1128/mbio.00637-26 |
| PMID: | 42565592 |
| Βάση Δεδομένων: | MEDLINE |
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