{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:58:21Z","timestamp":1789588701346,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T00:00:00Z","timestamp":1640822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator","award":["4500003336"],"award-info":[{"award-number":["4500003336"]}]},{"name":"ASPR\/BARDA","award":["IDSEP160030"],"award-info":[{"award-number":["IDSEP160030"]}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Award"],"award-info":[{"award-number":["Award"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Antimicrobial peptides (AMPs) have recently gained attention for their potential to treat diseases related to bacterial and viral infections, as many traditional antimicrobial drugs have reduced efficacy in treating these infections due to the increased prevalence of drug-resistant pathogens. PLG0206, an engineered cationic antibiotic peptide that is 24 residues long, has been designed to address some limitations of other natural AMPs, such as toxicity and limited activity due to pH and ion concentrations. Nonclinical studies have shown that PLG0206 is highly selective for targeting bacterial cells and is not toxic to human blood cells. Antibiofilm experiments demonstrated that PLG0206 is effective at reducing both biotic and abiotic biofilm burdens following direct biofilm contact. PLG0206 has rapid and broad-spectrum activity against both Gram-positive and Gram-negative bacteria that are implicated as etiologic agents in periprosthetic joint infections, including multidrug-resistant ESKAPE pathogens and colistin-resistant isolates. A recent first-in-human study demonstrated that PLG0206 is well tolerated and safe as an intravenous infusion in healthy volunteers. Studies are planned to determine the efficacy of PLG0206 in patients for the treatment of periprosthetic joint infections. This review summarizes the chemistry, pharmacology, and microbiology of PLG0206 and explores its current preclinical, clinical, and regulatory status.<\/jats:p>","DOI":"10.3390\/antibiotics11010041","type":"journal-article","created":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T21:41:21Z","timestamp":1640900481000},"page":"41","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Engineered Antibiotic Peptide PLG0206 Eliminates Biofilms and Is a Potential Treatment for Periprosthetic Joint Infections"],"prefix":"10.3390","volume":"11","author":[{"given":"David","family":"Huang","sequence":"first","affiliation":[{"name":"Peptilogics, 2730 Sidney Street, Suite 300, Pittsburgh, PA 15203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Pachuda","sequence":"additional","affiliation":[{"name":"Peptilogics, 2730 Sidney Street, Suite 300, Pittsburgh, PA 15203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Michael","family":"Sauer","sequence":"additional","affiliation":[{"name":"Peptilogics, 2730 Sidney Street, Suite 300, Pittsburgh, PA 15203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dessie","family":"Dobbins","sequence":"additional","affiliation":[{"name":"Peptilogics, 2730 Sidney Street, Suite 300, Pittsburgh, PA 15203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Steckbeck","sequence":"additional","affiliation":[{"name":"Peptilogics, 2730 Sidney Street, Suite 300, Pittsburgh, PA 15203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,30]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021, December 09). Antimicrobial Resistance. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/antimicrobial-resistance."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, C.H., and Lu, T.K. (2020). Development and Challenges of Antimicrobial Peptides for Therapeutic Applications. Antibiotics, 9.","DOI":"10.3390\/antibiotics9010024"},{"key":"ref_3","first-page":"1740","article-title":"Antimicrobial Peptides: A Potential Therapeutic Option for Surgical Site Infections","volume":"2","author":"Deslouches","year":"2017","journal-title":"Clin. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"582779","DOI":"10.3389\/fmicb.2020.582779","article-title":"Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields","volume":"11","author":"Huan","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.4049\/jimmunol.169.7.3883","article-title":"The Human Antimicrobial Peptide LL-37 is a Multifunctional Modulator of Innate Immune Responses","volume":"169","author":"Scott","year":"2002","journal-title":"J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.coph.2009.08.002","article-title":"New Approaches in Peptide Antibiotics","volume":"9","author":"Vaara","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3208","DOI":"10.1128\/AAC.49.8.3208-3216.2005","article-title":"Activity of the De Novo Engineered Antimicrobial Peptide WLBU2 against Pseudomonas aeruginosa in Human Serum and Whole Blood: Implications for Systemic Applications","volume":"49","author":"Deslouches","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.colsurfb.2014.05.004","article-title":"Binding Interactions of Bacterial Lipopolysaccharide and the Cationic Amphiphilic Peptides Polymyxin B and WLBU2","volume":"120","author":"Ryder","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1128\/AAC.49.1.316-322.2005","article-title":"De Novo Generation of Cationic Antimicrobial Peptides: Influence of Length and Tryptophan Substitution on Antimicrobial Activity","volume":"49","author":"Deslouches","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Deslouches, B., Montelaro, R.C., Urish, K.L., and Di, Y.P. (2020). Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12060501"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1128\/AAC.03937-14","article-title":"Engineered Cationic Antimicrobial Peptides to Overcome Multidrug Resistance by ESKAPE Pathogens","volume":"59","author":"Deslouches","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.arth.2017.11.029","article-title":"A Multicenter Study of Irrigation and Debridement in Total Knee Arthroplasty Periprosthetic Joint Infection: Treatment Failure Is High","volume":"33","author":"Urish","year":"2018","journal-title":"J. Arthroplast."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.arth.2020.12.005","article-title":"Projected Economic Burden of Periprosthetic Joint Infection of the Hip and Knee in the United States","volume":"36","author":"Premkumar","year":"2021","journal-title":"J. Arthroplast."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1128\/AAC.06246-11","article-title":"Microbiological Aetiology, Epidemiology, and Clinical Profile of Prosthetic Joint Infections: Are Current Antibiotic Prophylaxis Guidelines Effective?","volume":"56","author":"Peel","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/os.12394","article-title":"Identifying Common Pathogens in Periprosthetic Joint Infection and Testing Drug-Resistance Rate for Different Antibiotics: A Prospective, Single Center Study in Beijing","volume":"10","author":"Li","year":"2018","journal-title":"Orthop. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1128\/CMR.00111-13","article-title":"Prosthetic joint infection","volume":"27","author":"Tande","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/cis803","article-title":"Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guidelines by the Infectious Diseases Society of America","volume":"56","author":"Osmon","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.2106\/JBJS.L.00789","article-title":"Periprosthetic Joint Infection Increases the Risk of One-Year Mortality","volume":"95","author":"Zmistowski","year":"2013","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1007\/s11999-016-4720-8","article-title":"Antibiotic-Tolerant Staphylococcus aureus Biofilm Persists on Arthroplasty Materials","volume":"474","author":"Urish","year":"2016","journal-title":"Clin. Orthop Relat Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jot.2021.05.008","article-title":"Biofilm Properties in Relation to Treatment Outcome in Patients with First-time Periprosthetic Hip or Knee Joint Infection","volume":"30","author":"Tillander","year":"2021","journal-title":"J. Orthop. Translat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6247","DOI":"10.1002\/chem.202000212","article-title":"Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes","volume":"26","author":"Heinrich","year":"2020","journal-title":"Chemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1039\/C8SM02180E","article-title":"Elastic Behavior of Model Membranes with Antimicrobial Peptides Depends on Lipid Specificity and D-Enantiomers","volume":"15","author":"Kumagai","year":"2019","journal-title":"Soft Matter"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1128\/AAC.02218-12","article-title":"Rational Design of Engineered Cationic Antimicrobial Peptides Consisting Exclusively of Arginine and Tryptophan, and Their Activity against Multidrug-Resistant Pathogens","volume":"57","author":"Deslouches","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1016\/j.bbamem.2017.09.008","article-title":"Antimicrobial Peptides Are Degraded by the Cytosolic Proteases of Human Erythrocytes","volume":"1859","author":"Starr","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Huang, D., Dobbins, D., Ghahramani, P., Friedland, I., and Steckbeck, J. (2021). A Phase 1 Study of Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of a First in Human Engineered Cationic Peptide, PLG0206, Intravenously Administered in Healthy Subjects. Antimicrob. Agents Chemother., AAC0144121.","DOI":"10.1128\/AAC.01441-21"},{"key":"ref_26","unstructured":"Huang, D.P., Pachuda, N., and Sauer, J.M. (2016). Unpublished work."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"263","DOI":"10.2174\/1574884715666200810094201","article-title":"Mass Balance Study of the Engineered Cationic Antimicrobial Peptide, WLBU2, Following a Single Intravenous Dose of 14C-WLBU2 in Mice","volume":"16","author":"Beumer","year":"2021","journal-title":"Curr Rev. Clin. Exp. Pharmacol"},{"key":"ref_28","unstructured":"Investigator\u2019s Brochure for PLG0206 (2021). Unpublished work."},{"key":"ref_29","unstructured":"Murray, B.P., Hufnagel, D., and Pillar, C.M. (2020). In Vitro Activity of PLG0206 against a Representative Panel of Staphylococcus epidermidis and Other Coagulase-Negative Staphylococci, and Resistant Gram-Negative Pathogens, Unpublished work."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ijantimicag.2018.04.019","article-title":"Prevention of ESKAPE pathogen biofilm formation by antimicrobial peptides WLBU2 and LL37","volume":"52","author":"Lin","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.cmi.2014.10.024","article-title":"ESCMID Guideline for the Diagnosis and Treatment of Biofilm Infections 2014","volume":"21","author":"Hoiby","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.284.5418.1318","article-title":"Bacterial Biofilms: A Common Cause of Persistent Infections","volume":"284","author":"Costerton","year":"1999","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1093\/jac\/dkw143","article-title":"Engineered Cationic Antimicrobial Peptide (eCAP) Prevents Pseudomonas aeruginosa Biofilm Growth on Airway Epithelial Cells","volume":"71","author":"Lashua","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e00083-16","DOI":"10.1128\/mSphere.00083-16","article-title":"Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection","volume":"1","author":"Melvin","year":"2016","journal-title":"mSphere"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1002\/jor.24765","article-title":"Direct Antimicrobial Activity of Cationic Amphipathic Peptide WLBU2 Against Staphylococcus aureus Biofilms is Enhanced in Physiologic Buffered Saline","volume":"38","author":"Mandell","year":"2020","journal-title":"J. Orthop. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"18098","DOI":"10.1038\/s41598-017-17780-6","article-title":"Elimination of Antibiotic Resistant Surgical Implant Biofilms Using an Engineered Cationic Amphipathic Peptide WLBU2","volume":"7","author":"Mandell","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1302\/2046-3758.103.BJR-2019-0193.R3","article-title":"Development of a Large Animal Rabbit Model for Chronic Periprosthetic Joint Infection","volume":"10","author":"Yagi","year":"2021","journal-title":"Bone Jt. Res."},{"key":"ref_38","unstructured":"Brothers, K.M., Mandell, J.B., Taguchi, M., Parker, D.M., Alexander, P.G., Dobbins, D., Huang, D.B., Pachuda, N., and Urish, K.L. (2022, January 4\u20138). PLG0206, an Engineered Antimicrobial Peptide, has Potent Activity against Biofilm and Results in Disease Free Survival in a Rabbit Model of Staphylococcus aureus Periprosthetic Joint Infection. Proceedings of the 2022 Annual Meeting of the Orthopaedic Research Society, Tampa, FL, USA. accepted."},{"key":"ref_39","unstructured":"Mandell, J.B., Brothers, K., Shinaberger, D., Pillar, C., Huang, D., Steckbeck, J., and Urish, K.L. (2022, January 22\u201326). The Engineered Antimicrobial Peptide PLG0206 has High Biofilm and Planktonic Activity against Multi-Drug Resistant ESKAPE Organisms. Proceedings of the Annual Meeting of the American Academy of Orthopaedic Surgeons, Chicago, IL, USA. submitted."},{"key":"ref_40","unstructured":"Parker, D.M., Brothers, K.M., Mandell, J.B., Koch, J.A., Pachuda, N., Dobbins, D., Steckbeck, J., Huang, D.B., and Urish, K.L. (2022, January 4\u20138). Prospective Ex Vivo Activity of PLG0206, an Engineered Antimicrobial Peptide, on Chronic Periprosthetic Joint Infection Total Knee Arthroplasty Components: The Knee Explant Analysis (KnEA) Study. Proceedings of the 2022 Annual Meeting of the Orthopaedic Research Society, Tampa, FL, USA. accepted."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/1\/41\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:55:49Z","timestamp":1760169349000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/1\/41"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,30]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["antibiotics11010041"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics11010041","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,30]]}}}