The natural product, echinatin, protects mice from methicillin-resistant Staphylococcus aureus pneumonia by inhibition of alpha-hemolysin expression

Frontiers in Microbiology

Microbiology

Li Wang¹  Yicheng Zhao¹  Zhuoer Wang¹  Xin Ma²  Jiyu Guan³  Zhitong Tang⁴  Qing Gong⁴  Wei Zhang⁵  Ming Yan⁶ 

[1] Changchun University of Chinese Medicine, Changchun, China;Jilin Provincial Cancer Hospital, Changchun, China;Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China;The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China;The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China;The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China;College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, China;

关键词: antivirulence;    α-hemolysin;    Staphylococcus aureus;    pneumonia;    echinatin;   

DOI  :  10.3389/fmicb.2023.1128144

 received in 2022-12-20, accepted in 2023-03-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

Antimicrobial resistance (AMR) is a global, multifaceted crisis that poses significant challenges to the successful eradication of devastating pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), a persistent superbug that causes devastating infections. The scarcity of new antibacterial drugs is obvious, and antivirulence strategies that reduce the pathogenicity of bacteria by weakening their virulence have become the subject of intense investigation. Alpha-hemolysin (Hla), a cytolytic pore-forming toxin, has a pivotal role in S. aureus pathogenesis. Here, we demonstrated that echinatin, a natural compound isolated from licorice, effectively inhibited the hemolytic activity of MRSA at 32 μg/mL. In addition, echinatin did not interfere with bacterial growth and had no significant cytotoxicity at the inhibitory concentration of S. aureus hemolysis. Heptamer formation tightly correlated with Hla-mediated cell invasion, whereas echinatin did not affect deoxycholic acid-induced oligomerization of Hla. Echinatin affected hemolytic activity through indirect binding to Hla as confirmed by the neutralization assay and cellular thermal shift assay (CETSA). Furthermore, qRT–PCR and western blot analyses revealed that echinatin suppressed Hla expression at both the mRNA and protein levels as well as the transcript levels of Agr quorum-sensing system-related genes. Additionally, when echinatin was added to a coculture system of A549 cells and S. aureus, it significantly reduced cell damage. Importantly, echinatin exhibited a significant therapeutic effect in an MRSA-induced mouse pneumonia model. In conclusion, the present findings demonstrated that echinatin significantly inhibits the hemolysin effect and may be a potential candidate compound for combating drug-resistant MRSA infections.

【 授权许可】

Unknown   
Copyright © 2023 Zhang, Gong, Tang, Ma, Wang, Guan, Wang, Zhao and Yan.