{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:04:57Z","timestamp":1790053497464,"version":"4.0.1"},"reference-count":66,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Implant-associated infections are often caused by biofilm-forming pathogens such as Staphylococcus (S.) aureus. While local antibiotic delivery systems aim to prevent adhesion and biofilm establishment, declining drug concentrations may result in sub-inhibitory exposure, which can modulate bacterial adaptation linked to antibiotic resistance, biofilm formation, and regulatory responses. We investigated the effects of sub-inhibitory antibiotic exposure on biofilm formation in S. aureus SA113 and associated transcriptional responses. The biofilm-producing strain S. aureus SA113 was exposed to sub-inhibitory concentrations of rifampicin, minocycline, and dalbavancin during early biofilm formation. Phenotypic effects were assessed by crystal violet staining, enumeration of colony-forming units, and scanning electron microscopy, while transcriptional responses were analyzed by qPCR. Despite stable counts of culturable adherent bacteria, sub-inhibitory antibiotic exposure differentially altered biofilm formation and transcriptional responses. Rifampicin was associated with increased biomass at higher sub-inhibitory concentrations and increased early expression of icaA, icaD (+4.2 log2) and fnbA (+2.7 log2) at 1\/2\u00d7 MIC. Minocycline reduced biomass at lower concentrations with partial recovery toward control levels at 1\/2\u00d7 MIC, while transcriptional analysis at 1\/4\u00d7 MIC after 6 h showed increased expression of icaA, icaD (+2.1 log2) and fnbA (+4.3 log2). Dalbavancin induced a distinct transcriptional response characterized by increased expression of vraS (+1.1 log2) and lrgA (+1.8 log2), without induction of matrix-associated genes, while adherent biofilm biomass was reduced to 42.9% at 1\/2\u00d7 MIC. Morphologically, this was associated with compact aggregates rather than diffuse biofilm structures. Sub-inhibitory antibiotic exposure differentially modulated early biofilm formation in SA113 in a drug-specific manner. Overall, the distinct dalbavancin-associated response may be relevant for the development of preventive local drug-delivery systems.<\/jats:p>","DOI":"10.3390\/microorganisms14092101","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:25:43Z","timestamp":1789986343000},"page":"2101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Sub-Inhibitory Rifampicin, Minocycline, and Dalbavancin on Early Biofilm Formation and Transcriptional Responses in Staphylococcus aureus SA113"],"prefix":"10.3390","volume":"14","author":[{"given":"Adam","family":"Bieda","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, Nephrology, Endocrinology and Tropical Medicine, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2033-2964","authenticated-orcid":false,"given":"Sabine","family":"Illner","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering, University Medical Center Rostock, 18109 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9690-8416","authenticated-orcid":false,"given":"Volkmar","family":"Senz","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering, University Medical Center Rostock, 18109 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2339-456X","authenticated-orcid":false,"given":"Stefan","family":"Oschatz","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering, University Medical Center Rostock, 18109 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Grabow","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering, University Medical Center Rostock, 18109 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3453-8998","authenticated-orcid":false,"given":"Micha","family":"L\u00f6bermann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, Nephrology, Endocrinology and Tropical Medicine, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil Christian","family":"Reisinger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, Nephrology, Endocrinology and Tropical Medicine, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3861-0635","authenticated-orcid":false,"given":"Martina","family":"Sombetzki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, Nephrology, Endocrinology and Tropical Medicine, University Medical Center Rostock, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jhin.2012.09.005","article-title":"Early onset prosthetic hip and knee joint infection: Treatment and outcomes in Victoria, Australia","volume":"82","author":"Peel","year":"2012","journal-title":"J. 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