{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T04:11:11Z","timestamp":1774325471811,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Antimicrobial resistance (AMR) is a global, multifaceted crisis that poses significant challenges to the successful eradication of devastating pathogens, particularly methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (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 <jats:italic>S. aureus<\/jats:italic> pathogenesis. Here, we demonstrated that echinatin, a natural compound isolated from <jats:italic>licorice<\/jats:italic>, effectively inhibited the hemolytic activity of MRSA at 32\u2009\u03bcg\/mL. In addition, echinatin did not interfere with bacterial growth and had no significant cytotoxicity at the inhibitory concentration of <jats:italic>S. aureus<\/jats:italic> 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\u2013PCR 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 <jats:italic>S. aureus<\/jats:italic>, 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.<\/jats:p>","DOI":"10.3389\/fmicb.2023.1128144","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T04:24:02Z","timestamp":1681446242000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["The natural product, echinatin, protects mice from methicillin-resistant Staphylococcus aureus pneumonia by inhibition of alpha-hemolysin expression"],"prefix":"10.3389","volume":"14","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhitong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuoer","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyu","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yicheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e38567","DOI":"10.1371\/journal.pone.0038567","article-title":"Novel structurally designed vaccine for S. aureus \u03b1-hemolysin: Protection against bacteremia and pneumonia","volume":"7","author":"Adhikari","year":"2012","journal-title":"PLoS One"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1177\/2472555219883625","article-title":"A comparative study of target engagement assays for HDAC1 inhibitor profiling","volume":"25","author":"Asawa","year":"2020","journal-title":"SLAS Discov"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1128\/iai.01313-06","article-title":"Surface proteins and exotoxins are required for the pathogenesis of Staphylococcus aureus pneumonia","volume":"75","author":"Bubeck Wardenburg","year":"2007","journal-title":"Infect. 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