{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:14:13Z","timestamp":1792120453764,"version":"4.4.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p><jats:italic>Neisseria gonorrhoeae<\/jats:italic> is classified by the Centers for Disease Control and Prevention as an urgent public health threat due to rising infections and rapid resistance development. <jats:italic>N. gonorrhoeae<\/jats:italic> has developed resistance to nearly all FDA-approved drugs, with ceftriaxone being the only remaining effective treatment for gonococcal infections. Alarmingly, ceftriaxone-resistant <jats:italic>N. gonorrhoeae<\/jats:italic> strains were isolated worldwide, raising the potential of untreatable gonorrhea in the near future. Hence, the critical need to develop new anti-<jats:italic>N. gonorrhoeae<\/jats:italic> therapeutics cannot be overemphasized. In this study, we identified the peptide mimetic brilacidin as an effective anti-gonococcal agent. Brilacidin completed phase 2 clinical trials for treating skin infections, oral mucositis, and COVID-19. Herein, brilacidin displayed potent activity against a panel of 22 drug-resistant strains of <jats:italic>N. gonorrhoeae,<\/jats:italic> inhibiting 50% of the strains tested (MIC<jats:sub>50<\/jats:sub>) at the concentration of 4 \u00b5g\/mL. The peptide exhibited rapid bactericidal activity, reducing <jats:italic>N. gonorrhoeae<\/jats:italic> high inoculum within two hours. Moreover, brilacidin was superior to the drug of choice, ceftriaxone, in eliminating the intracellular <jats:italic>N. gonorrhoeae<\/jats:italic> harbored within endocervical cells. Additionally, brilacidin showed high tolerability in mammalian cells and lacked hemolytic activity in human erythrocytes. Altogether, the results demonstrate that brilacidin is a promising anti-gonococcal agent that warrants further in-depth investigation.<\/jats:p>","DOI":"10.1371\/journal.pone.0325722","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T17:37:42Z","timestamp":1749145062000},"page":"e0325722","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["A novel peptide mimetic, brilacidin, for combating multidrug-resistant Neisseria gonorrhoeae"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2902-3551","authenticated-orcid":true,"given":"Abdallah S.","family":"Abdelsattar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader S.","family":"Abutaleb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0939-0458","authenticated-orcid":true,"given":"Mohamed N.","family":"Seleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"issue":"12","key":"pone.0325722.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0143304","article-title":"Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting","volume":"10","author":"L Newman","year":"2015","journal-title":"PLoS One"},{"issue":"4","key":"pone.0325722.ref002","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/OLQ.0000000000001355","article-title":"Sexually Transmitted Infections Among US Women and Men: Prevalence and Incidence Estimates, 2018","volume":"48","author":"KM Kreisel","year":"2021","journal-title":"Sex Transm Dis"},{"key":"pone.0325722.ref003","year":"2022"},{"key":"pone.0325722.ref004"},{"key":"pone.0325722.ref005"},{"issue":"4","key":"pone.0325722.ref006","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1128\/CMR.17.4.965-981.2004","article-title":"The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women","volume":"17","author":"JL Edwards","year":"2004","journal-title":"Clin Microbiol Rev"},{"key":"pone.0325722.ref007","first-page":"197","article-title":"Gonorrhea infection in women: prevalence, effects, screening, and management","volume":"3","author":"CK Walker","year":"2011","journal-title":"Int J Womens Health"},{"issue":"6","key":"pone.0325722.ref008","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1097\/OLQ.0b013e318206c288","article-title":"The incidence and correlates of symptomatic and asymptomatic Chlamydia trachomatis and Neisseria gonorrhoeae infections in selected populations in five countries","volume":"38","author":"R Detels","year":"2011","journal-title":"Sex Transm Dis"},{"issue":"3","key":"pone.0325722.ref009","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1136\/sti.2009.037341","article-title":"A Bayesian approach to uncertainty analysis of sexually transmitted infection models","volume":"86","author":"LF Johnson","year":"2010","journal-title":"Sex Transm Infect"},{"issue":"2","key":"pone.0325722.ref010","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1258\/0956462021924712","article-title":"What proportion of episodes of gonorrhoea and chlamydia becomes symptomatic?","volume":"13","author":"EL Korenromp","year":"2002","journal-title":"Int J STD AIDS"},{"key":"pone.0325722.ref011","doi-asserted-by":"crossref","first-page":"100743","DOI":"10.1016\/j.lanepe.2023.100743","article-title":"Management of asymptomatic sexually transmitted infections in Europe: towards a differentiated, evidence-based approach","volume":"34","author":"C Kenyon","year":"2023","journal-title":"Lancet Reg Health Eur"},{"key":"pone.0325722.ref012","article-title":"2019 Antibiotic Resistance Threats Report.","volume-title":"Antimicrobial Resistance [Internet]","author":"CDC","year":"2024"},{"issue":"3","key":"pone.0325722.ref013","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1128\/AAC.05760-11","article-title":"High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure","volume":"56","author":"M Unemo","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"pone.0325722.ref014","doi-asserted-by":"crossref","first-page":"3538","DOI":"10.1128\/AAC.00325-11","article-title":"Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea? 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