ArticlePLoS pathogens2011
Small molecule inhibitors of Staphylococcus aureus RnpA alter cellular mRNA turnover, exhibit antimicrobial activity, and attenuate pathogenesis.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 64 citations in OpenAlex.
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- Molecular co-localization of multiple drugs in a nanoscopic delivery vehicle for potential synergistic remediation of multi-drug resistant bacteria.Scientific reports · 2022Article
- RNase P Inhibitors Identified as Aggregators.Antimicrobial agents and chemotherapy · 2021Article
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- Optimization of 2-Acylaminocycloalkylthiophene Derivatives for Activity againstAntibiotics (Basel, Switzerland) · 2021Article
- Dynamic insights on transcription initiation and RNA processing during bacterial adaptation.RNA (New York, N.Y.) · 2020Article
- Regulation of mRNA Stability During Bacterial Stress Responses.Frontiers in microbiology · 2020Review
- Breast Implant Surfaces and Their Impact on Current Practices: Where We Are Now and Where Are We Going?Plastic and reconstructive surgery. Global open · 2019Article
- A screening platform to monitor RNA processing and protein-RNA interactions in ribonuclease P uncovers a small molecule inhibitor.Nucleic acids research · 2019Article
- Identification of Small Molecule Inhibitors ofAntibiotics (Basel, Switzerland) · 2019Article
- Long Noncoding RNA SSR42 Controls Staphylococcus aureus Alpha-Toxin Transcription in Response to Environmental Stimuli.Journal of bacteriology · 2018Article
- Nonconventional Therapeutics againstMicrobiology spectrum · 2018Article
- Crystal structure of the ribonuclease-P-protein subunit from Staphylococcus aureus.Acta crystallographica. Section F, Structural biology communications · 2018Article
- Precision antimicrobial therapeutics: the path of least resistance?NPJ biofilms and microbiomes · 2018Review
- Article
- The Role of Ribonucleases and sRNAs in the Virulence of Foodborne Pathogens.Frontiers in microbiology · 2017Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 1 country.
Funding
Abstract
Methicillin-resistant Staphylococcus aureus is estimated to cause more U.S. deaths annually than HIV/AIDS. The emergence of hypervirulent and multidrug-resistant strains has further amplified public health concern and accentuated the need for new classes of antibiotics. RNA degradation is a required cellular process that could be exploited for novel antimicrobial drug development. However, such discovery efforts have been hindered because components of the Gram-positive RNA turnover machinery are incompletely defined. In the current study we found that the essential S. aureus protein, RnpA, catalyzes rRNA and mRNA digestion in vitro. Exploiting this activity, high through-put and secondary screening assays identified a small molecule inhibitor of RnpA-mediated in vitro RNA degradation. This agent was shown to limit cellular mRNA degradation and exhibited antimicrobial activity against predominant methicillin-resistant S. aureus (MRSA) lineages circulating throughout the U.S., vancomycin intermediate susceptible S. aureus (VISA), vancomycin resistant S. aureus (VRSA) and other Gram-positive bacterial pathogens with high RnpA amino acid conservation. We also found that this RnpA-inhibitor ameliorates disease in a systemic mouse infection model and has antimicrobial activity against biofilm-associated S. aureus. Taken together, these findings indicate that RnpA, either alone, as a component of the RNase P holoenzyme, and/or as a member of a more elaborate complex, may play a role in S. aureus RNA degradation and provide proof of principle for RNA catabolism-based antimicrobial therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.