ArticleNature microbiology2021
RNA antitoxin SprF1 binds ribosomes to attenuate translation and promote persister cell formation in Staphylococcus aureus.
Article in Nature microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- RefSeq-corrected transcriptomic and RNA-interaction integration maps medium-associated vancomycin response rewiring inFrontiers in microbiology · 2026Article
- Bistability in type I toxin-antitoxin systems may lead to stress-induced persister formation.NPJ systems biology and applications · 2025Article
- A host-directed adjuvant sensitizes intracellular bacterial persisters to antibiotics.Nature microbiology · 2025Article
- Development of a Potent and FunctionalJournal of medicinal chemistry · 2025Article
- Membrane selectivity and pore formation of SprA1 and SprA2 hemolytic peptides from Staphylococcus aureus type I toxin-antitoxin systems.The FEBS journal · 2025Article
- Analysis of co-occurrence of type II toxin-antitoxin systems and antibiotic resistance determinants inmSystems · 2025Article
- Characterization of a small non-coding RNA S612 inEngineering microbiology · 2025Article
- Insight into the environmental cues modulating the expression of bacterial toxin-antitoxin systems.FEMS microbiology reviews · 2025Review
- Regulatory RNAs inSynthetic and systems biotechnology · 2024Review
- Applications of toxin-antitoxin systems in synthetic biology.Engineering microbiology · 2023Review
- Success stories of natural product-derived compounds from plants as multidrug resistance modulators in microorganisms.RSC advances · 2023Review
- Comparative analysis of five type II TA systems identified inFrontiers in cellular and infection microbiology · 2023Article
- Bacterial toxin-antitoxin systems: Novel insights on toxin activation across populations and experimental shortcomings.Current research in microbial sciences · 2023Review
- Persistence of obligate intracellular pathogens: alternative strategies to overcome host-specific stresses.Frontiers in cellular and infection microbiology · 2023Review
- Mechanism of action ofFrontiers in microbiology · 2023Article
- The novel type II toxin-antitoxin PacTA modulates Pseudomonas aeruginosa iron homeostasis by obstructing the DNA-binding activity of Fur.Nucleic acids research · 2022Article
- Thirty Years of sRNA-Mediated Regulation inInternational journal of molecular sciences · 2022Review
- RNase III-CLASH of multi-drug resistant Staphylococcus aureus reveals a regulatory mRNA 3'UTR required for intermediate vancomycin resistance.Nature communications · 2022Article
- Ribosome-Associated ncRNAs (rancRNAs) Adjust Translation and Shape Proteomes.Non-coding RNA · 2022Review
- Targeting of Regulators as a Promising Approach in the Search for Novel Antimicrobial Agents.Microorganisms · 2022Article
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6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Persister cells are a subpopulation of transiently antibiotic-tolerant bacteria associated with chronic infection and antibiotic treatment failure. Toxin-antitoxin systems have been linked to persister cell formation but the molecular mechanisms leading to bacterial persistence are mostly unknown. Here, we show that SprF1, a type I antitoxin, associates with translating ribosomes from the major human pathogen Staphylococcus aureus to reduce the pathogen's overall protein synthesis during growth. Under hyperosmotic stress, SprF1 levels increase due to enhanced stability, accumulate on polysomes and attenuate protein synthesis. Using an internal 6-nucleotide sequence on its 5'-end, SprF1 binds ribosomes and interferes with initiator transfer RNA binding, thus reducing translation initiation. An excess of messenger RNA displaces the ribosome-bound antitoxin, freeing the ribosomes for new translation cycles; however, this RNA antitoxin can also displace ribosome-bound mRNA. This translation attenuation mechanism, mediated by an RNA antitoxin, promotes antibiotic persister cell formation. The untranslated SprF1 is a dual-function RNA antitoxin that represses toxin expression by its 3'-end and fine-tunes overall bacterial translation via its 5'-end. These findings demonstrate a general function for a bacterial RNA antitoxin beyond protection from toxicity. They also highlight an RNA-guided molecular process that influences antibiotic persister cell formation.
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