Disarming the Pathogenicity of Methicillin‐Resistant Staphylococcus aureus via Osmundacetone‐Mediated Inhibition of Sortase A
ABSTRACT Methicillin‐resistant Staphylococcus aureus (MRSA) is a major global health threat due to its resistance to multiple antibiotics, making conventional treatments ineffective. The rise in antibiotic resistance highlights the urgent need for new therapies. Sortase A (SrtA), a key virulence fac...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-05-01
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| Series: | Microbial Biotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1751-7915.70119 |
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| Summary: | ABSTRACT Methicillin‐resistant Staphylococcus aureus (MRSA) is a major global health threat due to its resistance to multiple antibiotics, making conventional treatments ineffective. The rise in antibiotic resistance highlights the urgent need for new therapies. Sortase A (SrtA), a key virulence factor in Staphylococcus aureus (S. aureus), facilitates bacterial adhesion and infection by anchoring surface proteins to host cells, making it a promising drug target. In this study, we investigated the potential of osmundacetone (OSC), a natural compound from Osmundae Rhizoma, as an SrtA inhibitor. Using fluorescence resonance energy transfer (FRET), OSC was found to inhibit SrtA with an IC50 of 1.29 μg/mL (7.24 μM). Further in vitro assays confirmed the effectiveness of OSC in inhibiting SrtA‐mediated bacterial adhesion, invasion and biofilm formation. Fluorescence quenching and molecular docking pinpointed the binding site of OSC on SrtA. In vivo, OSC improved survival rates in MRSA‐infected mice and Galleria mellonella (G. mellonella) while reducing bacterial loads in infected tissues. These results suggest OSC as a promising candidate for anti‐MRSA therapies. |
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| ISSN: | 1751-7915 |