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Daphnetin Prevents Methicillin-Resistant Staphylococcus Aureus Infection by Inducing Autophagic Response

Daphnetin Prevents Methicillin-Resistant Staphylococcus Aureus Infection by Inducing Autophagic Response

Wei Zhang, Shiqin Zhuo, Long He, Cheng Cheng, Bo Zhu, Yin Lu, Qinan Wu, Wenbin Shang, Weihong Ge, Liyun Shi

Int Immunopharmacol. 2019 Jul;72:195-203.

PMID: 30991161

Abstract:

The bacterial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) is a potentially fatal disease, featured with extensive infection, inflammation, and airway dysfunction. With the increasing emerging of drug-resistant strains, new therapeutic strategies beyond canonical antibiotic treatment are pressingly needed. Daphnetin (DAPH) is a natural coumarin derivative with anti-inflammation, anti-microorganism and anti-oxidative properties. However, the protective effect of DAPH on S. aureus-caused pneumonia and the mechanism involved are never explored. Here we show that DAPH treatment conferred substantial protection against S. aureus-induced pneumonia, characterized by the reduced inflammatory responses, the augmented bacterial clearance and the alleviated tissue damage. Our study indicates that DAPH significantly enhanced mTOR-dependent autophagic pathway, leading to the boosted microphage bactericidal activity and the suppressed inflammatory responses. Inhibition of autophagic pathway therefore largely abolished DAPH-elicited repression of inflammatory response and macrophage anti-bacterial capability. Together, we herein not only identify a novel, natural agent to combat bacterial pneumonia, but also underscore the significance of autophagic pathway in orchestrating antimicrobial and anti-inflammatory responses, which may have important implication for the treatment of the infectious diseases, particularly that caused by obstinate, antibiotic-resistant pathogens such as MRSA.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP145915588	DAPH		145915-58-8	Price

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