{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:41:32Z","timestamp":1784169692704,"version":"3.55.0"},"reference-count":22,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R41DE025789"],"award-info":[{"award-number":["R41DE025789"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R42DE025789"],"award-info":[{"award-number":["R42DE025789"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteomyelitis is a limb- and life-threatening orthopedic infection predominantly caused by Staphylococcus aureus biofilms. Bone infections are extremely challenging to treat clinically. Therefore, we have been designing, synthesizing, and testing novel antibiotic conjugates to target bone infections. This class of conjugates comprises bone-binding bisphosphonates as biochemical vectors for the delivery of antibiotic agents to bone minerals (hydroxyapatite). In the present study, we utilized a real-time impedance-based assay to study the growth of Staphylococcus aureus biofilms over time and to test the antimicrobial efficacy of our novel conjugates on the inhibition of biofilm growth in the presence and absence of hydroxyapatite. We tested early and newer generation quinolone antibiotics (ciprofloxacin, moxifloxacin, sitafloxacin, and nemonoxacin) and several bisphosphonate-conjugated versions of these antibiotics (bisphosphonate-carbamate-sitafloxacin (BCS), bisphosphonate-carbamate-nemonoxacin (BCN), etidronate-carbamate-ciprofloxacin (ECC), and etidronate-carbamate-moxifloxacin (ECX)) and found that they were able to inhibit Staphylococcus aureus biofilms in a dose-dependent manner. Among the conjugates, the greatest antimicrobial efficacy was observed for BCN with an MIC of 1.48 \u00b5g\/mL. The conjugates demonstrated varying antimicrobial activity depending on the specific antibiotic used for conjugation, the type of bisphosphonate moiety, the chemical conjugation scheme, and the presence or absence of hydroxyapatite. The conjugates designed and tested in this study retained the bone-binding properties of the parent bisphosphonate moiety as confirmed using high-performance liquid chromatography. They also retained the antimicrobial activity of the parent antibiotic in the presence or absence of hydroxyapatite, albeit at lower levels due to the nature of their chemical modification. These findings will aid in the optimization and testing of this novel class of drugs for future applications to pharmacotherapy in osteomyelitis.<\/jats:p>","DOI":"10.3390\/ijms24031985","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T05:06:14Z","timestamp":1674104774000},"page":"1985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Real-Time Impedance-Based Monitoring of the Growth and Inhibition of Osteomyelitis Biofilm Pathogen Staphylococcus aureus Treated with Novel Bisphosphonate-Fluoroquinolone Antimicrobial Conjugates"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4190-0497","authenticated-orcid":false,"given":"Parish P.","family":"Sedghizadeh","sequence":"first","affiliation":[{"name":"Division of Periodontology, Diagnostic Sciences and Dental Hygiene, Infection and Immunity Laboratory, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1070-6483","authenticated-orcid":false,"given":"Philip","family":"Cherian","sequence":"additional","affiliation":[{"name":"BioVinc LLC, Pasadena, CA 91107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Roshandel","sequence":"additional","affiliation":[{"name":"BioVinc LLC, Pasadena, CA 91107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Tjokro","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Diagnostic Sciences and Dental Hygiene, Infection and Immunity Laboratory, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Diagnostic Sciences and Dental Hygiene, Infection and Immunity Laboratory, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7559-8903","authenticated-orcid":false,"given":"Adam F.","family":"Junka","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology and Parasitology, Medical University of Wroclaw, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hu","sequence":"additional","affiliation":[{"name":"BioVinc LLC, Pasadena, CA 91107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Neighbors","sequence":"additional","affiliation":[{"name":"BioVinc LLC, Pasadena, CA 91107, USA"},{"name":"Department of Pharmacology and Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Pawlak","sequence":"additional","affiliation":[{"name":"Medical Department, Lazarski University, 02-662 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Graham G.","family":"Russell","sequence":"additional","affiliation":[{"name":"The Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX1 2JD, UK"},{"name":"The Mellanby Centre for Bone Research, Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"McKenna","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Southern California, Los Angeles, CA 90007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9133-1360","authenticated-orcid":false,"given":"Frank H.","family":"Ebetino","sequence":"additional","affiliation":[{"name":"BioVinc LLC, Pasadena, CA 91107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Sun","sequence":"additional","affiliation":[{"name":"BioVinc LLC, Pasadena, CA 91107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmat","family":"Sodagar","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Diagnostic Sciences and Dental Hygiene, Infection and Immunity Laboratory, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrmicro2415","article-title":"The biofilm matrix","volume":"8","author":"Flemming","year":"2010","journal-title":"Nat. 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