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At the heart of our study is the identification of a novel inhibitor through fluorescence anisotropy assays, specifically targeting the crucial multiple gene regulator A (MgrA) regulatory network in\n              <jats:italic>S. aureus<\/jats:italic>\n              . Isorhapontigenin (Iso), a natural compound, exhibits outstanding inhibitory efficacy, modulating bacterial virulence pathways without exerting direct bactericidal activity. This suggests a paradigm shift toward attenuating virulence instead of purely focusing on bacterial elimination. Through comprehensive\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              evaluations, we elucidated the complex interplay between Iso and MgrA, leading to reduced\n              <jats:italic>S. aureus<\/jats:italic>\n              adhesion, and overall virulence. At the cellular level, Iso offers significant protection to A549 cells infected with\n              <jats:italic>S. aureus<\/jats:italic>\n              , reducing cellular damage. Importantly, Iso augments the chemotaxis of neutrophils, curtailing the immune evasion capabilities of\n              <jats:italic>S. aureus<\/jats:italic>\n              . Furthermore,\n              <jats:italic>in vivo<\/jats:italic>\n              investigations highlight the notable effectiveness of Iso against MRSA-induced pneumonia and within the\n              <jats:italic>Galleria mellonella<\/jats:italic>\n              infection model, underscoring its pivotal role in the evolving realm of antibacterial drug discovery. Significantly, when Iso is used in combination with vancomycin, it outperforms its solo application, indicating a more pronounced therapeutic impact. This seminal research emphasizes Iso\u2019s potential as a primary defense against the surge of multidrug-resistant pathogens, heralding new prospects in antimicrobial therapy.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00611-24","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T13:02:52Z","timestamp":1721826172000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Elucidating the potential of isorhapontigenin in targeting the MgrA regulatory network: a paradigm shift for attenuating MRSA virulence"],"prefix":"10.1128","volume":"68","author":[{"given":"Lihan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Jilin University, Changchun, China"},{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9639-1058","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Medical College, Changchun University of Chinese Medicine, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Jilin University, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingmei","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Medical College, Changchun University of Chinese Medicine, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuerui","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Jilin University, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueshan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Jilin University, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1691-323X","authenticated-orcid":true,"given":"Yicheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Jilin University, Changchun, China"},{"name":"China-Japan Union Hospital of Jilin University, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0147-4"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03526.x"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3013"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3232"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.13.3703-3710.2003"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.027417-0"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio820"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3MR0320-444R"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1179403"},{"key":"e_1_3_4_11_2","volume-title":"Performance standards for antimicrobial susceptibility testing: twenty-third informational supplement","author":"El-Shaer S","year":"2017","unstructured":"El-Shaer S, Shaaban M, Barwa R, Hassan RHE. 2017. 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