ReferenceID 1005
Myricetin protects mice against MRSA-related lethal pneumonia by targeting ClpP
Biochem Pharmacol
Methicillin-resistant Staphylococcus aureus is one of the leading causes of community and nosocomial infections, which has created the urgent need for innovative anti-infective agents to control MRSA-associated infection
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Record Fields
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- Reference Id
- 1005
- Evidence Id
- 17595
- Core Evidence Id
- 17595
- Source Reference Id
- 2008
- Herb2 Reference Id
- HBREF002805
- Subject Paper Key
- HBIN007081_34474040
- Pubmed Id
- 34474040
- Doi
- 10.1016/j.bcp.2021.114753
- Paper Title
- Myricetin protects mice against MRSA-related lethal pneumonia by targeting ClpP
- Paper Abstract
- Methicillin-resistant Staphylococcus aureus is one of the leading causes of community and nosocomial infections, which has created the urgent need for innovative anti-infective agents to control MRSA-associated infections. A conserved serine protease, caseinolytic peptidase P (ClpP) in Staphylococcus aureus is highly associated with pathogenicity and has been claimed to be a novel antimicrobial target. We aim to search suitable inhibitors of ClpP to attenuate the virulence of MRSA and combat their infections in vivo. Over 500 natural compounds were pre-screened via fluorescence resonance energy transfer using the Suc-LY-AMC substrate. The binding of myricetin to ClpP was determined and the mechanism of action was elucidated by thermal shift assay, surface plasmon resonance, and molecular dynamics simulations. The therapeutic effects of myricetin on S. aureus infection were further investigated using a S. aureus-induced pneumonia model. We revealed that myricetin could effectively block the activity of ClpP without disturbing the growth of the bacteria and the Gln-47 and Met-31 residues were necessary for myricetin binding to ClpP. Importantly, myricetin attenuated the pathogenicity of S. aureus in vivo, while improving the efficacy of the traditional antibiotic oxacillin against MRSA infection and protecting mice from fatal lung infections caused by MRSA. These findings indicate that myricetin has the potential to be applied in the pharmaceutical industry as a promising therapeutic agent.
- Journal
- Biochem Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Fatal Lung Infections; S. Aureus-induced Pneumonia; Nosocomial Infections
- Paper Title Cn
- Paper Title En
- Myricetin protects mice against MRSA-related lethal pneumonia by targeting ClpP
- Bilingual Status
- semi_complete