Brazilin reduces methicillin-resistant Staphylococcus aureus virulence and pathogenicity by decreasing the secretion of the α-hemolysin

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-03-07 DOI:10.1016/j.phymed.2025.156616

Mingzhe Li , Zhengyuan An , Mengfei Yu , Xiaoxian Zhou , Zhifang Yang , Zehui Chen

{"title":"Brazilin reduces methicillin-resistant Staphylococcus aureus virulence and pathogenicity by decreasing the secretion of the α-hemolysin","authors":"Mingzhe Li , Zhengyuan An , Mengfei Yu , Xiaoxian Zhou , Zhifang Yang , Zehui Chen","doi":"10.1016/j.phymed.2025.156616","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) is a super-resistant bacterium with strong pathogenicity, causing broad range of infections in various tissues. α-Hemolysin (Hla) is the main virulence factor of <em>S. aureus</em>. Brazilin (BN), is a homoisoflavonoid derivative, obtained from the wood of <em>Caesalpinia echinata</em> Lam (Brazil-wood), <em>Caesalpinia sappan</em> L (Leguminosae), and <em>Caesalpinia violacea</em> Standl, has been proven to exert excellent antibacterial and anti-virulence effects against <em>S. aureus</em>. However, the underlying mechanisms remain still unclear.</div></div><div><h3>Objective</h3><div>This study aims to evaluate the inhibitory effect of BN on MRSA virulence and pathogenicity and elucidate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>Rabbit erythrocytes were used to evaluate the effect of BN on hemocytolysis. The potential target of BN was screened by transcriptomic sequencing and verified by qRT-PCR, western blot (WB), and molecular interaction experiments. The effects of BN on MRSA toxicity and pathogenicity were both validated using A549 cell and mouse skin abscess model caused by MRSA.</div></div><div><h3>Results</h3><div>BN attenuated the hemolytic activity of MRSA by inhibiting Hla secretion. It was also found that BN blocks its binding to the P1 promoter of the <em>sae</em> operon, and then reduced its transcript level. Remarkably, <em>ΔsaeR</em> strain exhibits significantly reduced hemolytic activity due to impaired regulation of Hla and no extra inhibitory effect was observed in the samples treated with BN. Moreover, BN relieved A549 cell damage and mouse skin abscess induced by MRSA by inhibiting SaeR.</div></div><div><h3>Conclusion</h3><div>These findings reveal, for the first time, BN can alleviate MRSA virulence and pathogenicity by decreasing the secretion of the Hla <em>via</em> inhibiting SaeR. Overall, this study suggests that BN could be a candidate for being submitted to further studies with the aim of its development as a new antibiotic against MRSA.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156616"},"PeriodicalIF":6.7000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0944711325002569","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is a super-resistant bacterium with strong pathogenicity, causing broad range of infections in various tissues. α-Hemolysin (Hla) is the main virulence factor of S. aureus. Brazilin (BN), is a homoisoflavonoid derivative, obtained from the wood of Caesalpinia echinata Lam (Brazil-wood), Caesalpinia sappan L (Leguminosae), and Caesalpinia violacea Standl, has been proven to exert excellent antibacterial and anti-virulence effects against S. aureus. However, the underlying mechanisms remain still unclear.

Objective

This study aims to evaluate the inhibitory effect of BN on MRSA virulence and pathogenicity and elucidate its underlying mechanisms.

Methods

Rabbit erythrocytes were used to evaluate the effect of BN on hemocytolysis. The potential target of BN was screened by transcriptomic sequencing and verified by qRT-PCR, western blot (WB), and molecular interaction experiments. The effects of BN on MRSA toxicity and pathogenicity were both validated using A549 cell and mouse skin abscess model caused by MRSA.

Results

BN attenuated the hemolytic activity of MRSA by inhibiting Hla secretion. It was also found that BN blocks its binding to the P1 promoter of the sae operon, and then reduced its transcript level. Remarkably, ΔsaeR strain exhibits significantly reduced hemolytic activity due to impaired regulation of Hla and no extra inhibitory effect was observed in the samples treated with BN. Moreover, BN relieved A549 cell damage and mouse skin abscess induced by MRSA by inhibiting SaeR.

Conclusion

These findings reveal, for the first time, BN can alleviate MRSA virulence and pathogenicity by decreasing the secretion of the Hla via inhibiting SaeR. Overall, this study suggests that BN could be a candidate for being submitted to further studies with the aim of its development as a new antibiotic against MRSA.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.