{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:05:59Z","timestamp":1790719559431,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["5K08AR069112-01"],"award-info":[{"award-number":["5K08AR069112-01"]}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["T32AR059033"],"award-info":[{"award-number":["T32AR059033"]}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["R44AI150143"],"award-info":[{"award-number":["R44AI150143"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["5K08AR069112-01"],"award-info":[{"award-number":["5K08AR069112-01"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["T32AR059033"],"award-info":[{"award-number":["T32AR059033"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["R44AI150143"],"award-info":[{"award-number":["R44AI150143"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Bacterial biofilms on orthopedic implants are resistant to the host immune response and to traditional systemic antibiotics. Novel therapies are needed to improve patient outcomes. TRL1068 is a human monoclonal antibody (mAb) against a biofilm anchoring protein. For assessment of this agent in an orthopedic implant infection model, efficacy was measured by reduction in bacterial burden of Staphylococcus aureus, the most common pathogen for prosthetic joint infections (PJI). Systemic treatment with the biofilm disrupting mAb TRL1068 in conjunction with vancomycin eradicated S. aureus from steel pins implanted in the spine for 26 of 27 mice, significantly more than for vancomycin alone. The mechanism of action was elucidated by two microscopy studies. First, TRL1068 was localized to biofilm using a fluorescent antibody tag. Second, a qualitative effect on biofilm structure was observed using scanning electron microscopy (SEM) to examine steel pins that had been treated in vivo. SEM images of implants retrieved from control mice showed abundant three-dimensional biofilms, whereas those from mice treated with TRL1068 did not. Clinical Significance: TRL1068 binds at high affinity to S. aureus biofilms, thereby disrupting the three-dimensional structure and significantly reducing implant CFUs in a well-characterized orthopedic model for which prior tested agents have shown only partial efficacy. TRL1068 represents a promising systemic treatment for orthopedic implant infection.<\/jats:p>","DOI":"10.3390\/antibiotics12101490","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T05:55:54Z","timestamp":1695880554000},"page":"1490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Monoclonal Antibody Disrupts Biofilm Structure and Restores Antibiotic Susceptibility in an Orthopedic Implant Infection Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-0956","authenticated-orcid":false,"given":"Zachary D. C.","family":"Burke","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Orthopaedic Surgery, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7889-7407","authenticated-orcid":false,"given":"Benjamin V.","family":"Kelley","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Kavanaugh","sequence":"additional","affiliation":[{"name":"Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Tenorio","sequence":"additional","affiliation":[{"name":"Trellis Bioscience, Inc., Redwood City, CA 94063, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence M.","family":"Kauvar","sequence":"additional","affiliation":[{"name":"Trellis Bioscience, Inc., Redwood City, CA 94063, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, 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