期刊
MICROBIOLOGICAL RESEARCH
卷 261, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.micres.2022.127071
关键词
Staphylococcus aureus; alpha-hemolysin; Hispidulin; Quorum sensing; Pneumonia
类别
资金
- Science and Technology Development Plan Project of Jilin Province Science and Technology Department [20190103080JH]
- ''Xinglin Scholar Project of Changchun University of Chinese Medicine [QNKXJ2-2021ZR05]
- Thirteenth Five-Year Plan of Science and Technology Project of Education Department of Jilin Province [JJKH20200906KJ]
Hispidulin effectively inhibits the expression of the virulence factor alpha-hemolysin in Staphylococcus aureus without affecting bacterial growth.
The emergence of drug-resistant Staphylococcus aureus (S. aureus) has limited drug options for the clinical treatment of S. aureus infections. Considering recent reports, therapeutic strategies targeting bacterial virulence hold great promise, and alpha-hemolysin (encoded by hla), a critical virulence factor of S. aureus, plays a vital role during bacterial infection. Herein, we demonstrated that hispidulin effectively inhibited the hemolytic activity of S. aureus USA300 without suppressing bacterial growth, along with inhibiting hla transcription and expression in a dose-dependent manner. As heptamer formation is essential for hla-mediated invasion of cells, nevertheless, hispidulin did not affect the deoxycholate-induced oligomerization of hla, suggesting that hispidulin did not affect the protein activity of hla. In vitro assays illustrated that hispidulin bound to agrA(C), a crucial protein in quorum sensing. Meanwhile, hispidulin alleviated A549 cell damage caused by S. aureus USA300 and reduced lactate dehydrogenase release. In vivo studies showed that hispidulin had a protective effect against pneumonia caused by S. aureus USA300 in mice. S. aureus did not develop resistance to hispidulin in the short term. Interestingly, our research indicated that hispidulin synergized with the antibacterial activity of cefoxitin. These results showed that hispidulin effectively inhibited alpha-hemolysin expression by inhibiting the agr quorum sensing of S. aureus. It has promise as an agent to treat S. aureus infection.
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