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Elucidating the potential of isorhapontigenin in targeting the MgrA regulatory network: a paradigm shift for attenuating MRSA virulence
As methicillin-resistant (MRSA) exhibits formidable resistance to many drugs, the imperative for alternative therapeutic strategies becomes increasingly evident. At the heart of our study is the identification of a novel inhibitor through fluorescence anisotropy assays, specifically targeting the cr...
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Published in: | Antimicrobial agents and chemotherapy 2024-09, Vol.68 (9), p.e0061124 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | As methicillin-resistant
(MRSA) exhibits formidable resistance to many drugs, the imperative for alternative therapeutic strategies becomes increasingly evident. At the heart of our study is the identification of a novel inhibitor through fluorescence anisotropy assays, specifically targeting the crucial multiple gene regulator A (MgrA) regulatory network in
. Isorhapontigenin (Iso), a natural compound, exhibits outstanding inhibitory efficacy, modulating bacterial virulence pathways without exerting direct bactericidal activity. This suggests a paradigm shift toward attenuating virulence instead of purely focusing on bacterial elimination. Through comprehensive
and
evaluations, we elucidated the complex interplay between Iso and MgrA, leading to reduced
adhesion, and overall virulence. At the cellular level, Iso offers significant protection to A549 cells infected with
, reducing cellular damage. Importantly, Iso augments the chemotaxis of neutrophils, curtailing the immune evasion capabilities of
. Furthermore,
investigations highlight the notable effectiveness of Iso against MRSA-induced pneumonia and within the
infection model, underscoring its pivotal role in the evolving realm of antibacterial drug discovery. Significantly, when Iso is used in combination with vancomycin, it outperforms its solo application, indicating a more pronounced therapeutic impact. This seminal research emphasizes Iso's potential as a primary defense against the surge of multidrug-resistant pathogens, heralding new prospects in antimicrobial therapy. |
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ISSN: | 0066-4804 1098-6596 1098-6596 |
DOI: | 10.1128/aac.00611-24 |