{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:16:56Z","timestamp":1783487816559,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007932","name":"Gansu Agricultural University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007932","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The SaeRS two-component system is a major virulence regulator in\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      , and its sensor kinase SaeS represents a potential target for small-molecule intervention.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we constructed a library of 1,093 compounds from PubChem and carried out structure-guided virtual screening against the SaeS kinase domain. This approach identified an amide-based candidate, designated Saeamid-1. Molecular docking and molecular dynamics simulations supported stable binding of Saeamid-1 within the nucleotide-binding region of SaeS, with a docking score of -9.884 kcal\/mol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The compound had only limited effects on bacterial growth. In contrast, it reduced hemolytic activity and biofilm biomass in USA300 by 65.74% and 88.77%, respectively. RT-qPCR analysis showed that Saeamid-1 reduced the expression of\n                      <jats:italic>saeR, saeS<\/jats:italic>\n                      , and the\n                      <jats:italic>SaeRS-<\/jats:italic>\n                      associated virulence gene\n                      <jats:italic>spa<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Taken together, these findings identify Saeamid-1 as a promising antivirulence candidate that targets SaeS in methicillin-resistant\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      and provide a basis for further development of therapeutic strategies directed against the SaeRS pathway.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1867130","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:48:49Z","timestamp":1783486129000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel SaeS-targeting antivirulence antagonist screened against methicillin-resistant Staphylococcus aureus"],"prefix":"10.3389","volume":"16","author":[{"given":"Jiahao","family":"Yao","sequence":"first","affiliation":[{"name":"College of Food Science and Engineering, Gansu Agricultural University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duiyuan","family":"Ai","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Gansu Agricultural University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Duan","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Gansu Agricultural University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"Abraham","year":"2015","journal-title":"Softwarex"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0325830","article-title":"In silico analysis of quorum sensing modulators: Insights into molecular docking and dynamics and potential therapeutic applications","volume":"20","author":"Alisaac","year":"2025","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1268044","article-title":"Identification of an antivirulence agent targeting the master regulator of virulence genes in Staphylococcus aureus","volume":"13","author":"Arya","year":"2023","journal-title":"Front. 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