{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:47:10Z","timestamp":1785113230494,"version":"3.55.0"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sichuan Provincial Natural Science Foundation of China","award":["2019YFS0270; 2021YJ0455"],"award-info":[{"award-number":["2019YFS0270; 2021YJ0455"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Staphylococcus aureus (S. aureus) is one of most common opportunistic pathogens and is attributed to several human infections. The increasing incidence of methicillin-resistant S. aureus (MRSA) is a serious clinical threat for osteomyelitis crisis. The YycFG two-component system of S. aureus regulates genes associated with biofilm formation. To investigate the potential role of an antisense yycF RNA in the regulation of transcription levels of yycF and associated effects on biofilm formation and pathogenicity, antisense yycF (ASyycF) RNA was detected by RT-PCR and 5\u2032 RACE assays. ASyycF overexpression mutants were constructed, and the biofilm biomass was determined by crystal violet microtiter assay and scanning electron microscopy (SEM). Quantitative RT-PCR and Western blotting analyses were used to detect whether ASyycF overexpression inhibited the transcription and translation of biofilm-related genes. Then, a rat tibial infective model was used to evaluate the pathogenicity of ASyycF overexpression in vivo. ASyycF transcription led to reductions in YycF production and biofilm formation. Overexpression of ASyycF inhibited the transcription and translation of biofilm-related genes. The sensitivity to vancomycin was improved in ASyycF-overexpressing MRSA. Furthermore, ASyycF inhibited MRSA invasion in a rat tibial infection model. From this study, the expression of the YycF protein was found to be inversely correlated with different levels of ASyycF transcription. The biofilm biomass and pathogenicity decreased in the ASyycF-overexpressing mutant. Thus, the current evidence may support ASyycF as a supplementary strategy for managing S. aureus and MRSA infections.<\/jats:p>","DOI":"10.3390\/antibiotics10050603","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T12:58:07Z","timestamp":1621429087000},"page":"603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["An Antisense yycF RNA Modulates Biofilm Organization of Methicillin-Resistant Staphylococcus aureus and Pathogenicity in a Rat Model of Osteomyelitis"],"prefix":"10.3390","volume":"10","author":[{"given":"Shizhou","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1292\/jvms.19-0216","article-title":"A new transformation method with nanographene oxides of antisense carrying yycG RNA improved antibacterial properties on methicillin-resistant Staphylococcus aureus biofilm","volume":"81","author":"Wu","year":"2019","journal-title":"J. Vet. Med. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.2147\/IDR.S272733","article-title":"Methicillin-Resistant Staphylococcus aureus (MRSA): One Health Perspective Approach to the Bacterium Epidemiology, Virulence Factors, Antibiotic-Resistance, and Zoonotic Impact","volume":"13","author":"Algammal","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1302\/2046-3758.92.BJR-2019-0131.R1","article-title":"Recalcitrant methicillin-resistant Staphylococcus aureus infection of bone cells: Intracellular penetration and control strategies","volume":"9","author":"Yu","year":"2020","journal-title":"Bone Jt. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jayakumar, J., Kumar, V.A., Biswas, L., and Biswas, R. (2020). Therapeutic applications of lysostaphin against Staphylococcus aureus. J. Appl. Microbiol.","DOI":"10.1111\/jam.14985"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M. (2019). The Continuing Threat of Methicillin-Resistant Staphylococcus aureus. Antibiotics, 8.","DOI":"10.3390\/antibiotics8020052"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13018-018-1055-z","article-title":"Staphylococcus aureus biofilm organization modulated by YycFG two-component regulatory pathway","volume":"14","author":"Wu","year":"2019","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mosselhy, D.A., Assad, M., Sironen, T., and Elbahri, M. (2021). Nanotheranostics: A Possible Solution for Drug-Resistant Staphylococcus aureus and their Biofilms?. Nanomaterials, 11.","DOI":"10.3390\/nano11010082"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12951-020-00760-w","article-title":"Surface charge modulation of rifampicin-loaded PLA nanoparticles to improve antibiotic delivery in Staphylococcus aureus biofilms","volume":"19","author":"Rambaud","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1016\/j.csbj.2020.10.027","article-title":"The staphylococcal exopolysaccharide PIA\u2014Biosynthesis and role in biofilm for-mation, colonization, and infection","volume":"18","author":"Nguyen","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1089\/sur.2019.016","article-title":"Antisense yycG Regulation of Antibiotic Sensitivity of Methicillin-Resistant Staphylococcus aureus in Chronic Osteomyelitis","volume":"20","author":"Wu","year":"2019","journal-title":"Surg. Infect. (Larchmt)"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2217\/fmb-2019-0002","article-title":"Roles of two-component regulatory systems in antibiotic resistance","volume":"14","author":"Tierney","year":"2019","journal-title":"Future Microbiol."},{"key":"ref_12","first-page":"5","article-title":"Two-component signaling pathways modulate drug resistance of Staphylococcus aureus (Review)","volume":"13","author":"Wu","year":"2020","journal-title":"Biomed. Rep."},{"key":"ref_13","first-page":"e00511","article-title":"Systematic Reconstruction of the Complete Two-Component Sensorial Network in Staphylococcus aureus","volume":"5","author":"Haag","year":"2020","journal-title":"mSystems"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41467-018-02949-y","article-title":"Sensory deprivation in Staphylococcus aureus","volume":"9","author":"Villanueva","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3892\/etm.2020.9501","article-title":"Endogenous antisense walR RNA modulates biofilm organization and pathogenicity of Enterococcus faecalis","volume":"21","author":"Wu","year":"2020","journal-title":"Exp. Ther. Med"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1177\/0022034518781765","article-title":"Activity of Streptococcus mutans VicR Is Modulated by An-tisense RNA","volume":"97","author":"Lei","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00018","DOI":"10.1128\/CMR.00020-18","article-title":"Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epide-miology","volume":"31","author":"Lakhundi","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ijantimicag.2006.09.001","article-title":"Costs of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) and its control","volume":"28","author":"Gould","year":"2006","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijmm.2018.11.002","article-title":"An update on recent developments in the prevention and treatment of Staphylococcus aureus biofilms","volume":"309","author":"Suresh","year":"2019","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/lam.13354","article-title":"Nanographene oxides carrying antisense walR RNA regulates the Enterococcus faecalis biofilm formation and its susceptibility to chlorhexidine","volume":"71","author":"Wu","year":"2020","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Uru\u00e9n, C., Chopo-Escuin, G., Tommassen, J., Mainar-Jaime, R.C., and Arenas, J. (2020). Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance. Antibiotics, 10.","DOI":"10.3390\/antibiotics10010003"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1128\/JCM.37.6.1771-1776.1999","article-title":"The Calgary Biofilm Device: New Technology for Rapid Determination of Antibiotic Susceptibilities of Bacterial Biofilms","volume":"37","author":"Ceri","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1093\/cid\/cit614","article-title":"Methicillin-Resistant Staphylococcus aureus Therapy: Past, Present, and Future","volume":"58","author":"Rodvold","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1080\/1040841X.2017.1282941","article-title":"The role of biofilms in persistent infections and factors in-volved in ica-independent biofilm development and gene regulation in Staphylococcus aureus","volume":"43","author":"Figueiredo","year":"2017","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jcma.2017.07.012","article-title":"Bacterial biofilm and associated infections","volume":"81","author":"Jamal","year":"2018","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e01910","DOI":"10.1128\/mBio.01910-14","article-title":"Clinical Characteristics and Outcomes of Prosthetic Joint Infection Caused by Small Colony Variant Staphylococci","volume":"5","author":"Tande","year":"2014","journal-title":"mBio"},{"key":"ref_27","first-page":"1","article-title":"Virulence of methicillin-resistant Staphylococcus aureus modulated by the YycFG two-component pathway in a rat model of osteomyelitis","volume":"14","author":"Wu","year":"2019","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_28","first-page":"1","article-title":"The Pathogenicity and Transcriptome Analysis of Methicillin-Resistant Staphylococcus aureus in Response to Water Extract of Galla chinensis","volume":"2019","author":"Wu","year":"2019","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.12669\/pjms.37.1.2887","article-title":"Efficacy of vancomycin in combination with various antimicrobial agents against clinical methicillin resistant Staphylococcus aureus strains","volume":"37","author":"Aktas","year":"2020","journal-title":"Pak. J. Med. Sci."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/5\/603\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:04:02Z","timestamp":1760162642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/5\/603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,19]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["antibiotics10050603"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10050603","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,19]]}}}