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Updated: Mar 3, 2026
08:25
Inactivation of Pathogens via Visible-Light Photolysis of Riboflavin-5′-Phosphate
Published on: April 6, 2022
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Dual-Targeting Small-Molecule Inhibitors of the Staphylococcus aureus FMN Riboswitch Disrupt Riboflavin Homeostasis
Hao Wang1, Paul A Mann1, Li Xiao1
1Merck Research Laboratories, Kenilworth, NJ 07033, USA.
Cell Chemical Biology
|April 25, 2017
Summary
Riboswitches control bacterial gene expression. Inhibitors like ribocil-C and roseoflavin target flavin mononucleotide (FMN) riboswitches, offering a new strategy against Gram-positive bacteria, including MRSA.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Riboswitches are conserved non-coding RNA elements regulating bacterial gene expression.
- Inhibitors of riboswitches represent a novel class of antibacterial agents.
- Flavin mononucleotide (FMN) riboswitches control essential metabolic pathways and transport functions.
Purpose of the Study:
- To mechanistically characterize the antibacterial effects of ribocil-C and roseoflavin (RoF).
- To investigate the efficacy of these compounds against medically significant Gram-positive bacteria, including MRSA and Enterococcus faecalis.
- To explore a dual-targeting mechanism for broad-spectrum antibacterial agents.
Main Methods:
- Genetic analysis
- Biophysical characterization
- Computational modeling
- Biochemical assays
- Pharmacological studies
Main Results:
- Ribocil-C and RoF specifically inhibit dual FMN riboswitches in Gram-positive bacteria.
- These FMN riboswitches control both riboflavin biosynthesis and uptake.
- The dual-targeting mechanism is essential for inhibiting MRSA growth and pathogenesis.
Conclusions:
- Ribocil-C and RoF demonstrate potential as antibacterial agents by targeting FMN riboswitches.
- Dual inhibition of riboflavin metabolism pathways is a viable strategy against Gram-positive pathogens.
- This approach is crucial for developing broad-spectrum antibiotics targeting RF metabolism.
Keywords:
Enterococcus faecalisFMN riboswitchMRSARibUStaphylococcus aureusantibiotic drug targetribocilriboflavinroseoflavinvirulence factorMore Related Videos
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