Key result
Novel carba-sugar analogue activates S. aureus glmS-riboswitch at 6.24 μM, matching native metabolite potency.
Why the study?
The glmS-riboswitch of Staphylococcus aureus is a promising antibiotic target due to its role in cell wall biosynthesis and unique metabolite-dependent self-cleavage activity.
A newly synthesized carba-sugar activates the glmS-riboswitch of vancomycin-resistant S. aureus, providing a lead structure for novel antibiotics.
Hypothesis-generating for glmS-riboswitch activators against resistant S. aureus; leaves open in vivo efficacy and clinical translation.
The glmS-riboswitch is unique among riboswitch families as it represents a metabolite-dependent ribozyme that undergoes self-cleavage upon recognition of glucosamin-6-phosphate. The glmS-riboswitch is located in the 5'-untranslated region of bacterial genes involved in cell wall biosynthesis. Therefore, this riboswitch represents a promising target for developing new antibiotics. We describe the metabolite-dependent glmS-riboswitch of pathologically relevant and vancomycin-resistant Staphylococcus aureus and the discovery and synthesis of a carba-sugar with potency similar to that of the native metabolite glucosamine-6-phosphate in modulating riboswitch activity. This compound represents a valuable lead structure for the development of antibiotics with a novel mode of action.
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Schmidt et al. (2011) conducted a letter in Staphylococcus aureus (in vitro). Carba-sugar 8 (carba-GlcN6P) vs. Glucosamine-6-phosphate (GlcN6P) was evaluated on Riboswitch activation (EC50 in μM). A novel carba-sugar analogue (compound 8) activated the metabolite-dependent glmS-riboswitch from Staphylococcus aureus with an EC50 of 6.24 μM, demonstrating similar potency to the native metabolite.
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