{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:31:31Z","timestamp":1787725891496,"version":"build-2784847793"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Antimicrobial resistance among Gram-negative bacteria, particularly\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      ,\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      ,\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      , and\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                      , has reduced the effectiveness of conventional antibiotics. Biofilm formation further increases bacterial tolerance and exacerbates resistance to multiple antibiotics. Pyocins, bacteriocins produced by\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      , are emerging as promising targeted antibacterial and antibiofilm agents. However, there is no comprehensive systematic literature synthesis of pyocin extraction, characterization, antibacterial, and antibiofilm efficacy against a wide range of Gram-negative biofilm-forming pathogens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To systematically evaluate evidence on the extraction, purification, characterization, antibacterial activity, antibiofilm efficacy, and resistance mechanisms of pyocins against Gram-negative bacteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This review followed PRISMA 2020 guidelines and was registered in PROSPERO (ID: CRD420251064333). PubMed, Scopus, Web of Science, and CINAHL databases were searched for studies published between January 2015 and June 2025. Eligible studies included\n                      <jats:italic>in vitro<\/jats:italic>\n                      and preclinical investigations of S-, R-, F-type, or recombinant pyocins. Data on antibacterial activity and antibiofilm outcomes were extracted. Risk of bias was assessed using an adapted ROBINS-E framework. Findings were synthesized narratively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 191 records were identified; 137 were screened after duplicate removal, and 7 studies met the inclusion criteria. Pyocins demonstrated strong antibacterial activity against\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      , with minimum inhibitory concentration values as low as 0.003\u202f\u03bcg\/mL. Antibiofilm effects ranged from 48 to 84% reduction, with enhanced activity when combined with enzymes, particularly glycoside hydrolases. Mechanisms of action included membrane depolarization, pore formation, and receptor-mediated uptake. Resistance mechanisms involved lipopolysaccharide modification, receptor mutation, and immunity proteins. Overall risk of bias was low to moderate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Pyocins exhibit potent antibacterial and antibiofilm activity and represent promising alternatives to conventional antibiotics. However, standardized methodologies,\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation, and clinical studies are needed to support their therapeutic application.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1878395","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:03:36Z","timestamp":1787724216000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibacterial and antibiofilm activities of pyocins produced by Pseudomonas aeruginosa against gram-negative bacteria: a systematic review (2015\u20132025)"],"prefix":"10.3389","volume":"17","author":[{"given":"Sekari","family":"Hickson","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Life Sciences, University of Maiduguri","place":["Maiduguri, Borno State, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atinga","family":"Atimi","sequence":"additional","affiliation":[{"name":"Department of Public Health, Faculty of Health Sciences, Taraba State College of Health Technology","place":["Takum, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Mustapha","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Life Sciences, University of Maiduguri","place":["Maiduguri, Borno State, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abubakar","family":"Shettima","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Life Sciences, University of Maiduguri","place":["Maiduguri, Borno State, Nigeria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrakib","family":"Abdulrahim","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia","place":["Serdang, Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ukpai","family":"Eze","sequence":"additional","affiliation":[{"name":"Chester Medical School, Faculty of Health, Medicine and Society, University of Chester, CH21BR","place":["Chester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref1","volume-title":"Host-Pathogen Interactions","author":"Abedon","year":"2018"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1139\/cjm-2021-0207","article-title":"Recombinant R2-pyocin cream is effective in treating Pseudomonas aeruginosa- infected wounds","volume":"67","author":"Alqahtani","year":"2021","journal-title":"Can. J. Microbiol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e03230-19","DOI":"10.1128\/mBio.03230-19","article-title":"Pyocin S5 import into Pseudomonas aeruginosa reveals a generic mode of bacteriocin transport","volume":"11","author":"Behrens","year":"2020","journal-title":"MBio"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1042\/ETLS20160016","article-title":"The therapeutic potential of bacteriocins as protein antibiotics","volume":"1","author":"Behrens","year":"2017","journal-title":"Emerg. Topics in Life Sci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/apm.12099","article-title":"The role of bacterial biofilms in chronic infections","volume":"121","author":"Bjarnsholt","year":"2013","journal-title":"APMIS"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/nrmicro3380","article-title":"Molecular mechanisms of antibiotic resistance","volume":"13","author":"Blair","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1128\/MMBR.00036-06","article-title":"Colicin biology","volume":"71","author":"Cascales","year":"2007","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S1473-3099(18)30605-4","article-title":"Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European economic area in 2015: a population-level modelling analysis","volume":"19","author":"Cassini","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/s41579-022-00682-4","article-title":"Tolerance and resistance of microbial biofilms","volume":"20","author":"Ciofu","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1002\/mbo3.339","article-title":"Identification and functional analysis of a bacteriocin, pyocin S6, with ribonuclease activity from a Pseudomonas aeruginosa cystic fibrosis clinical isolate","volume":"5","author":"Dingemans","year":"2016","journal-title":"MicrobiologyOpen."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/microorganisms5020015","article-title":"Approaches to dispersing medical biofilms","volume":"5","author":"Fleming","year":"2017","journal-title":"Microorganisms."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nrmicro2415","article-title":"The biofilm matrix","volume":"8","author":"Flemming","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.cmi.2015.12.002","article-title":"The negative impact of antibiotic resistance","volume":"22","author":"Friedman","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1111\/1574-6976.12079","article-title":"Ribosomally encoded antibacterial proteins and peptides from Pseudomonas","volume":"38","author":"Ghequire","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e33033","DOI":"10.1371\/journal.pone.0033033","article-title":"Ferredoxin containing bacteriocins suggest a novel mechanism of iron uptake in Pectobacterium spp","volume":"7","author":"Grinter","year":"2012","journal-title":"PLoS One"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e1566","DOI":"10.1002\/hsr2.1566","article-title":"Antibiotic resistance and the COVID-19 pandemic: a dual crisis with complex challenges in LMICs","volume":"6","author":"Gulumbe","year":"2023","journal-title":"Health Sci. Reports."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/nrmicro821","article-title":"Bacterial biofilms: from the natural environment to infectious diseases","volume":"2","author":"Hall-Stoodley","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref9001","doi-asserted-by":"publisher","first-page":"108602","DOI":"10.1016\/j.envint.2024.108602","article-title":"A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E)","volume":"186","author":"Higgins","year":"2024","journal-title":"Environment International"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"61","DOI":"10.24126\/jobrc.2025.19.1.923","article-title":"Antibiofilm activity of pyocin against local isolates of Pseudomonas aeruginosa","volume":"19","author":"Khalaf","year":"2025","journal-title":"J. Biotechnol. Res. Center"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nrmicro2315","article-title":"Bacteriophage resistance mechanisms","volume":"8","author":"Labrie","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1128\/MMBR.00013-14","article-title":"Biofilm-related infections: bridging the gap between clinical management and fundamental aspects of recalcitrance toward antibiotics","volume":"78","author":"Lebeaux","year":"2014","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"S37","DOI":"10.1016\/S0924-8579(12)70008-0","article-title":"Epidemiology and antimicrobial susceptibility profiles of gram-negative bacteria causing urinary tract infections in the Asia-Pacific region: 2009\u20132010 results from the study for monitoring antimicrobial resistance trends (SMART)","volume":"40","author":"Lu","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e1003898","DOI":"10.1371\/journal.ppat.1003898","article-title":"Lectin-like bacteriocins from Pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor","volume":"10","author":"McCaughey","year":"2014","journal-title":"PLoS Pathog."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"30201","DOI":"10.1038\/srep30201","article-title":"Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection","volume":"6","author":"McCaughey","year":"2016","journal-title":"Sci. Rep."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e00458-21","DOI":"10.1128\/mBio.00458-21","article-title":"Heterogenous susceptibility to R-pyocins in populations of Pseudomonas aeruginosa sourced from cystic fibrosis lungs","volume":"12","author":"Mei","year":"2021","journal-title":"MBio"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/S0300-9084(02)01422-0","article-title":"The pyocins of Pseudomonas aeruginosa","volume":"84","author":"Michel-Briand","year":"2002","journal-title":"Biochimie"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00248-013-0297-x","article-title":"Pseudomonas aeruginosa biofilms in disease","volume":"68","author":"Mulcahy","year":"2014","journal-title":"Microb. Ecol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e1012933","DOI":"10.1371\/journal.ppat.1012933","article-title":"Alternative lipid synthesis in response to phosphate limitation promotes antibiotic tolerance in gram-negative ESKAPE pathogens","volume":"21","author":"Olea-Ozuna","year":"2025","journal-title":"PLoS Pathog."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e01828-18","DOI":"10.1128\/mBio.01828-18","article-title":"Competition in biofilms between cystic fibrosis isolates of Pseudomonas aeruginosa is shaped by R-pyocins","volume":"10","author":"Oluyombo","year":"2019","journal-title":"MBio"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2770","DOI":"10.1093\/jac\/dky261","article-title":"Susceptibility to R-pyocins of Pseudomonas aeruginosa clinical isolates from cystic fibrosis patients","volume":"73","author":"Redero","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e00029-23","DOI":"10.1128\/jb.00029-23","article-title":"F-type pyocins are diverse noncontractile phage tail-like weapons for killing Pseudomonas aeruginosa","volume":"205","author":"Saha","year":"2023","journal-title":"J. Bacteriol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1146\/annurev-virology-101416-041632","article-title":"Phage tail\u2013like bacteriocins","volume":"4","author":"Scholl","year":"2017","journal-title":"Annu. Rev. Virol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1128\/AAC.01479-07","article-title":"Antibacterial efficacy of R-type Pyocins towards Pseudomonas aeruginosa in a murine peritonitis model","volume":"52","author":"Scholl","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"i4919","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/nrmicro1838","article-title":"Physiological heterogeneity in biofilms","volume":"6","author":"Stewart","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s12874-021-01295-w","article-title":"Quality assessment tools used in systematic reviews of in vitro studies: a systematic review","volume":"21","author":"Tran","year":"2021","journal-title":"BMC Med. Res. Methodol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"3868","DOI":"10.1128\/AEM.00141-08","article-title":"Retargeting R-type pyocins to generate novel bactericidal protein complexes","volume":"74","author":"Williams","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"ref39","volume-title":"WHO Bacterial Priority Pathogens list, 2024: Bacterial Pathogens of public Health Importance to guide Research, Development and Strategies to Prevent and Control Antimicrobial Resistance","year":"2024"},{"key":"ref40","volume-title":"Antimicrobial resistance","year":"2023"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1878395\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:03:38Z","timestamp":1787724218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1878395\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":41,"alternative-id":["10.3389\/fmicb.2026.1878395"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1878395","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"article-number":"1878395"}}