{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:29:56Z","timestamp":1790188196569,"version":"4.1.0"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32071341"],"award-info":[{"award-number":["32071341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32101062"],"award-info":[{"award-number":["32101062"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Orthopedic device-related infection (ODRI) caused by <jats:italic>Staphylococcus aureus<\/jats:italic>, especially methicillin-resistant <jats:italic>S. aureus<\/jats:italic> (MRSA) biofilm may lead to persist infection and severe inflammatory osteolysis. Previous studies have demonstrated that both isobavachalcone and curcumin possess antimicrobial activity, recent studies also reveal their antiosteoporosis, anti-inflammation, and immunoregulatory effect. Thus, this study aims to investigate whether the combination of isobavachalcone and curcumin can enhance the anti-<jats:italic>S. aureus<\/jats:italic> biofilm activity of gentamicin and alleviate inflammatory osteolysis <jats:italic>in vivo<\/jats:italic>. EUCAST and a standardized MBEC assay were used to verify the synergy between isobavachalcone and curcumin with gentamicin against planktonic <jats:italic>S. aureus<\/jats:italic> and its biofilm <jats:italic>in vitro<\/jats:italic>, then the antimicrobial and immunoregulatory effect of cocktail therapy was demonstrated in a femoral ODRI mouse model <jats:italic>in vivo<\/jats:italic> by \u03bcCT analysis, histopathology, quantification of bacteria in bone and myeloid-derived suppressor cell (MDSC) in bone marrow. We tested on standard MSSA ATCC25923 and MRSA USA300, 5 clinical isolated MSSA, and 2 clinical isolated MRSA strains and found that gentamicin with curcumin (62.5\u2013250\u2009\u03bcg\/ml) and gentamicin with isobavachalcone (1.56\u2009\u03bcg\/ml) are synergistic against planktonic MSSA, while gentamicin (128\u2009\u03bcg\/ml) with curcumin (31.25\u201362.5, 250\u2013500\u2009\u03bcg\/ml) and gentamicin (64\u2013128\u2009\u03bcg\/ml) with isobavachalcone (1.56\u201312.5\u2009\u03bcg\/ml) exhibit synergistic effect against MSSA biofilm. Results of further study revealed that cocktail of 128\u2009\u03bcg\/ml gentamicin together with 125\u2009\u03bcg\/ml curcumin +6.25\u2009\u03bcg\/ml isobavachalcone showed promising biofilm eradication effect with synergy against USA300 biofilm <jats:italic>in vitro<\/jats:italic>. Daily intraperitoneal administration of 20\u2009mg\/kg\/day isobavachalcone, 20\u2009mg\/kg\/day curcumin, and 20\u2009mg\/kg\/day gentamicin, can reduce inflammatory osteolysis and maintain microarchitecture of trabecular bone during orthopedic device-related MRSA infection in mice. Cocktail therapy also enhanced reduction of MDSC M1 polarization in peri-implant tissue, suppression of MDSC amplification in bone marrow, and Eradication of USA300 biofilm <jats:italic>in vivo<\/jats:italic>. Together, these results suggest that the combination of isobavachalcone and curcumin as adjuvants administrated together with gentamicin significantly enhances its antimicrobial effect against <jats:italic>S. aureus<\/jats:italic> biofilm, and can also modify topical inflammation in ODRI and protect bone microstructure <jats:italic>in vivo<\/jats:italic>, which may serve as a potential treatment strategy, especially for <jats:italic>S. aureus<\/jats:italic> induced ODRI.<\/jats:p>","DOI":"10.3389\/fmicb.2022.958132","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T06:59:14Z","timestamp":1663916354000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Cocktail of isobavachalcone and curcumin enhance eradication of Staphylococcus aureus biofilm from orthopedic implants by gentamicin and alleviate inflammatory osteolysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Yan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangli","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zemin","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bizhi","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingxuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuenong","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"528","DOI":"10.7326\/0003-4819-89-4-528","article-title":"Gentamicin in 1978","volume":"89","author":"Appel","year":"1978","journal-title":"Ann. 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