{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T14:15:42Z","timestamp":1764080142606,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Maryland, Baltimore","award":["1UL1TR003098"],"award-info":[{"award-number":["1UL1TR003098"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background:\u00a0Staphylococcus aureus necrotizing fasciitis is a life-threatening infection requiring aggressive surgical and medical management. Despite these interventions, tremendous morbidity and mortality occur. Thus, novel agents are needed to reduce these negative outcomes. Consequently, the aims of this translational study were to evaluate the feasibility of using bacteriophages and the potential clinical ramifications of using bacteriophages in treatment of S. aureus necrotizing fasciitis. Methods: Necrotizing fasciitis clinical isolates (n = 6) were tested against different Staphylococcal bacteriophages (n = 4) to assess for activity. After exposure to bacteriophages that had growth inhibition for more than 16 h, the ability of S. aureus to change phenotypic expression of numerous enzymes was evaluated, and the ability to reduce bacterial virulence was measured with the Caenorhabditis elegans assay. Results: Staphylococcal myoviridae bacteriophages were able to lyse most clinical isolates (83%). Interestingly, after exposure to myoviridae bacteriophages, S. aureus isolates had no expression of hemolysin, secreted coagulase, or lecthinase, or the ability to ferment mannitol. These same bacteriophages also caused statistically significant decreases in bacterial virulence (p &lt; 0.05). Neither findings were observed for bacteriophages of the podoviridae family. Conclusions: To use bacteriophages for S. aureus necrotizing fasciitis, cocktails of Staphylococcal myoviridae are likely needed to allow for broad host ranges, mitigating the need for in vitro sensitivity testing. Moreover, Staphylococcal myoviridae have the potential to reduce specific enzyme expression and global virulence of residual S. aureus. Thus, bacteriophages may aid in reducing necrotizing fasciitis morbidity by not only lysing S. aureus but also by reducing S. aureus virulence.<\/jats:p>","DOI":"10.3390\/jcm14165609","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T09:56:42Z","timestamp":1754647002000},"page":"5609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Feasibility and Potential Clinical Ramifications of Using Bacteriophage Therapy for S. aureus Necrotizing Fasciitis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-0968","authenticated-orcid":false,"given":"James B.","family":"Doub","sequence":"first","affiliation":[{"name":"The Doub Laboratory of Translational Bacterial Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8326-9131","authenticated-orcid":false,"given":"Dakarai","family":"Dunbar","sequence":"additional","affiliation":[{"name":"Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2391-3155","authenticated-orcid":false,"given":"Sara","family":"Jain","sequence":"additional","affiliation":[{"name":"Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie","family":"Manchester","sequence":"additional","affiliation":[{"name":"Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3642-1793","authenticated-orcid":false,"given":"Lila","family":"Berle","sequence":"additional","affiliation":[{"name":"Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janvi","family":"Madhiwala","sequence":"additional","affiliation":[{"name":"Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2237-8672","authenticated-orcid":false,"given":"Bradley","family":"Anderson","sequence":"additional","affiliation":[{"name":"Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riva","family":"Malick","sequence":"additional","affiliation":[{"name":"Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Jacobs","sequence":"additional","affiliation":[{"name":"The Doub Laboratory of Translational Bacterial Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth L.","family":"Urish","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.idc.2017.05.011","article-title":"Evaluation and Management of Necrotizing Soft Tissue Infections","volume":"31","author":"Bonne","year":"2017","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/QCO.0000000000000988","article-title":"Necrotizing fasciitis: An update on epidemiology, diagnostic methods, and treatment","volume":"37","author":"Allaw","year":"2024","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_3","first-page":"981","article-title":"Necrotizing fasciitis","volume":"55","author":"Puvanendran","year":"2009","journal-title":"Can. Fam. Physician"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.amsu.2015.07.017","article-title":"Intravenous immunoglobulin in necrotizing fasciitis\u2014A case report and review of recent literature","volume":"4","author":"Koch","year":"2015","journal-title":"Ann. Med. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1001\/jamasurg.2024.3365","article-title":"Necrotizing Soft Tissue Infections: A Review","volume":"159","author":"McDermott","year":"2024","journal-title":"JAMA Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1089\/sur.2023.353","article-title":"Is Prompt Hyperbaric Oxygen Adjunctive Therapy Able to Reduce Mortality and Amputation in Management of Necrotizing Soft-Tissue Infection?","volume":"25","author":"Chiang","year":"2024","journal-title":"Surg. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"756","DOI":"10.2340\/17453674.2022.4579","article-title":"Salphage: Salvage bacteriophage therapy for a recalcitrant Klebsiella pneumoniae prosthetic shoulder infection\u2014A case report","volume":"93","author":"Doub","year":"2022","journal-title":"Acta Orthop."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s10096-023-04658-x","article-title":"Bacteriophage therapy: Are we running before we have learned to walk?","volume":"42","author":"Doub","year":"2023","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.mib.2014.11.009","article-title":"Microbial pathogenesis and host defense in the nematode C. elegans","volume":"23","author":"Cohen","year":"2015","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kamaladevi, A., and Balamurugan, K. (2014). Response of Caenorhabditis elegans during Klebsiella pneumoniae pathogenesis. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-S3-P8"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e0207121","DOI":"10.1128\/aac.02071-21","article-title":"Antibacterial Resistance Leadership Group. Considerations for the Use of Phage Therapy in Clinical Practice","volume":"66","author":"Suh","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijid.2022.03.022","article-title":"Impact of Bacterial Phenotypic Variation with Bacteriophage therapy: A Pilot Study with Prosthetic Joint Infection Isolates","volume":"119","author":"Doub","year":"2022","journal-title":"Int. J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Moller, A.G., Lindsay, J.A., and Read, T.D. (2019). Determinants of Phage Host Range in Staphylococcus Species. Appl. Environ. Microbiol., 85.","DOI":"10.1128\/AEM.00209-19"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4279","DOI":"10.1007\/s00253-019-09810-2","article-title":"Peculiarities of Staphylococcus aureus phages and their possible application in phage therapy","volume":"103","author":"Azam","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e0187921","DOI":"10.1128\/AAC.01879-21","article-title":"Phage Activity against Planktonic and Biofilm Staphylococcus aureus Periprosthetic Joint Infection Isolates","volume":"66","author":"Totten","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Egido, J.E., Costa, A.R., Aparicio-Maldonado, C., Haas, P.J., and Brouns, S.J.J. (2022). Mechanisms and clinical importance of bacteriophage resistance. FEMS Microbiol. Rev., 46.","DOI":"10.1093\/femsre\/fuab048"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"dlae017","DOI":"10.1093\/jacamr\/dlae017","article-title":"Improving phage therapy by evasion of phage resistance mechanisms","volume":"6","author":"Bleriot","year":"2024","journal-title":"JAC Antimicrob Resist."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Brignoli, T., Douglas, E., Duggan, S., Fagunloye, O.G., Adhikari, R., Aman, M.J., and Massey, R.C. (2022). Wall Teichoic Acids Facilitate the Release of Toxins from the Surface of Staphylococcus aureus. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.01011-22"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wanner, S., Schade, J., Keinh\u00f6rster, D., Weller, N., George, S.E., Kull, L., Bauer, J., Grau, T., Winstel, V., and Stoy, H. (2017). Wall teichoic acids mediate increased virulence in Staphylococcus aureus. Nat. Microbiol., 2.","DOI":"10.1038\/nmicrobiol.2016.257"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sharma, S., Singh, K., Chaurasiya, A., Banerjee, T., Singh, R., Yadav, G., and Kumar, A. (2025). Comparative study of phenotypic and genotypic expression of virulence factors in colonizing and pathogenic carbapenem resistant Acinetobacter baumannii (CRAB). BMC Microbiol., 25.","DOI":"10.1186\/s12866-024-03727-1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/978-1-0716-4100-2_12","article-title":"Zebrafish Larvae Microinjection and Automated Fluorescence Microscopy for Studying Klebsiella pneumoniae Infection and the Host Immune Response","volume":"2852","author":"Varas","year":"2025","journal-title":"Methods Mol. Biol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/16\/5609\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:26:07Z","timestamp":1760034367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/16\/5609"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":21,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["jcm14165609"],"URL":"https:\/\/doi.org\/10.3390\/jcm14165609","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,8,8]]}}}