{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T17:23:00Z","timestamp":1789320180714,"version":"build-2803163510"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"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:p>\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    is a versatile opportunistic pathogen whose capacity to form biofilms contributes to persistent and difficult-to-treat infections, particularly in clinical environments. Conventional antibiotics often fail to eliminate biofilm-embedded bacteria, highlighting the need for alternative therapeutic strategies. Here, we investigated the anti-biofilm activity of Stigmurin, an antimicrobial peptide identified in the venom of\n                    <jats:italic>Tityus stigmurus<\/jats:italic>\n                    , together with six lysine-enriched analogs. The peptides were synthesized and characterized at a physicochemical level, and their effects on bacterial growth, biofilm development, and disruption of pre-established biofilms were evaluated under both static and dynamic conditions. Their influence on pyocyanin production, membrane fluidity, and the tridimensional structure of the most active analog, StigA31, was also analyzed. The peptides revealed no marked impact on bacterial growth or biofilm formation. However, several of them were able to disrupt mature biofilms on polystyrene pegs. Stigmurin (24 h exposition) reduced biofilm biomass by nearly 47%, while StigA31 achieved dispersal levels of up to 35%, even at nanomolar concentrations. Under dynamic flow conditions, both peptides strongly reduced biofilm biovolume and thickness within 2 h and altered matrix exopolysaccharide detection. None of the compounds stimulated pyocyanin production. Stigmurin altered membrane fluidity, whereas StigA31 displayed a distinct mechanism that may be associated with its helical conformation. These findings indicate that Stigmurin analogs, particularly StigA31, promote P. aeruginosa biofilm dispersal through non-bactericidal mechanisms. Their activity at sub-inhibitory concentrations highlights their potential as promising candidates for use in strategies aimed at controlling biofilm-associated infections.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1827386","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:17:27Z","timestamp":1779949047000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Stigmurin derivatives as potent-biofilm eradicating agents against the major human opportunistic pathogen Pseudomonas aeruginosa"],"prefix":"10.3389","volume":"17","author":[{"given":"Anne-Sophie","family":"Tareau","sequence":"first","affiliation":[{"name":"Univ Rouen Normandie, Universit\u00e9 Caen Normandie, Normandie Univ, CBSA","place":["Rouen, UR, France"]},{"name":"Univ Rouen Normandie, Platform of Sanitary Safety, Evreux Campus","place":["Evreux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Marina e Silva","family":"Parente","sequence":"additional","affiliation":[{"name":"Biotechnology Laboratory in Biomolecules (LBB), Department of Biochemistry, Center for Biosciences, Federal University of Rio Grande do Norte (UFRN)","place":["Natal, RN, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allanny Alves","family":"Furtado","sequence":"additional","affiliation":[{"name":"Biotechnology Laboratory in Biomolecules (LBB), Department of Biochemistry, Center for Biosciences, Federal University of Rio Grande do Norte (UFRN)","place":["Natal, RN, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magalie","family":"Barreau","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Universit\u00e9 Caen Normandie, Normandie Univ, CBSA","place":["Rouen, UR, France"]},{"name":"Univ Rouen Normandie, Platform of Sanitary Safety, Evreux Campus","place":["Evreux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung","family":"Le","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Universit\u00e9 Caen Normandie, Normandie Univ, CBSA","place":["Rouen, UR, France"]},{"name":"Univ Rouen Normandie, Platform of Sanitary Safety, Evreux Campus","place":["Evreux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Amorim-Carmo","sequence":"additional","affiliation":[{"name":"Biotechnology Laboratory in Biomolecules (LBB), Department of Biochemistry, Center for Biosciences, Federal University of Rio Grande do Norte (UFRN)","place":["Natal, RN, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Hil\u00e1rio Nogueira","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Isolation and Synthesis of Organic Compounds, Department of Biochemistry, Institute of Chemistry, Federal University of Rio Grande do Norte (UFRN)","place":["Natal, RN, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Maillot","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Universit\u00e9 Caen Normandie, Normandie Univ, CBSA","place":["Rouen, UR, France"]},{"name":"Univ Rouen Normandie, Platform of Sanitary Safety, Evreux Campus","place":["Evreux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Universit\u00e9 Caen Normandie, Normandie Univ, CBSA","place":["Rouen, UR, France"]},{"name":"Univ Rouen Normandie, Platform of Sanitary Safety, Evreux Campus","place":["Evreux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Forge","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Universit\u00e9 Caen Normandie, Normandie Univ, CBSA","place":["Rouen, UR, France"]},{"name":"Univ Rouen Normandie, Platform of Sanitary Safety, Evreux Campus","place":["Evreux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Tahrioui","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Universit\u00e9 Caen Normandie, Normandie Univ, CBSA","place":["Rouen, UR, France"]},{"name":"Univ Rouen Normandie, Platform of Sanitary Safety, Evreux Campus","place":["Evreux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarbas Magalhaes","family":"Resende","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese e Estrutura de Pept\u00eddeos, Departamento de Qu\u00edmica, Universidade Federal de Minas Gerais","place":["Belo Horizonte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lesouhaitier","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Universit\u00e9 Caen Normandie, Normandie Univ, CBSA","place":["Rouen, UR, France"]},{"name":"Univ Rouen Normandie, Platform of Sanitary Safety, Evreux Campus","place":["Evreux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Mendon\u00e7a Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Isolation and Synthesis of Organic Compounds, Department of Biochemistry, Institute of Chemistry, Federal University of Rio Grande do Norte (UFRN)","place":["Natal, RN, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus de Freitas","family":"Fernandes-Pedrosa","sequence":"additional","affiliation":[{"name":"Biotechnology Laboratory in Biomolecules (LBB), Department of Biochemistry, Center for Biosciences, Federal University of Rio Grande do Norte (UFRN)","place":["Natal, RN, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Chevalier","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, Universit\u00e9 Caen Normandie, Normandie Univ, CBSA","place":["Rouen, UR, France"]},{"name":"Univ Rouen Normandie, Platform of Sanitary Safety, Evreux Campus","place":["Evreux, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1186\/1471-2164-13-362","article-title":"Profiling the resting venom gland of the scorpion Tityus stigmurus through a transcriptomic survey","volume":"13","author":"Almeida","year":"2012","journal-title":"BMC Genomics"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"4600","DOI":"10.1128\/JB.00707-13","article-title":"The putative Enoyl-coenzyme a hydratase DspI is required for production of the Pseudomonas aeruginosa biofilm dispersion autoinducer cis \u22122-Decenoic acid","volume":"195","author":"Amari","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"623","DOI":"10.3390\/ijms20030623","article-title":"Potent and broad-Spectrum antimicrobial activity of analogs from the scorpion peptide Stigmurin","volume":"20","author":"Amorim-Carmo","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"887763","DOI":"10.3389\/fmolb.2022.887763","article-title":"Antimicrobial peptide analogs from scorpions: modifications and structure-activity","volume":"9","author":"Amorim-Carmo","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1080\/1040841X.2016.1208146","article-title":"Critical review on biofilm methods","volume":"43","author":"Azeredo","year":"2017","journal-title":"Crit. Rev. Microbiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.3390\/biom10121626","article-title":"Tackling Pseudomonas aeruginosa virulence by Mulinane-like Diterpenoids from Azorella atacamensis","volume":"10","author":"Azuama","year":"2020","journal-title":"Biomolecules"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/0022-2364(85)90018-6","article-title":"MLEV-17-based two-dimensional homonuclear magnetization transfer spectroscopy","volume":"65","author":"Bax","year":"1985","journal-title":"J. Magnet. Res."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"9050","DOI":"10.1021\/acs.jmedchem.2c00270","article-title":"Antimicrobial peptides against multidrug-resistant Pseudomonas aeruginosa biofilm from cystic fibrosis patients","volume":"65","author":"Ben Hur","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1128\/JB.01034-13","article-title":"Identification of the alternative sigma factor SigX regulon and its implications for Pseudomonas aeruginosa pathogenicity","volume":"196","author":"Blanka","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e84775","DOI":"10.1371\/journal.pone.0084775","article-title":"A novel role for an ECF sigma factor in fatty acid biosynthesis and membrane fluidity in Pseudomonas aeruginosa","volume":"8","author":"Boechat","year":"2013","journal-title":"PLoS One"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1128\/AAC.02676-15","article-title":"Evolution of Pseudomonas aeruginosa antimicrobial resistance and fitness under low and high mutation rates","volume":"60","author":"Cabot","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e12667","DOI":"10.7717\/peerj.12667","article-title":"Antimicrobial peptides properties beyond growth inhibition and bacterial killing","volume":"10","author":"Castillo-Ju\u00e1rez","year":"2022","journal-title":"PeerJ"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1128\/JB.00595-18","article-title":"Genomic and phenotypic diversity among ten Laboratory isolates of Pseudomonas aeruginosa PAO1","volume":"201","author":"Chandler","year":"2019","journal-title":"J. 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Acta"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/978-3-031-08491-1_6","article-title":"Cell Envelope Stress Response in Pseudomonas aeruginosa","volume":"1386","author":"Chevalier","year":"2022","journal-title":"Advances in experimental medicine and biology,"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"4462","DOI":"10.1038\/ncomms5462","article-title":"Dispersed cells represent a distinct stage in the transition from bacterial biofilm to planktonic lifestyles","volume":"5","author":"Chua","year":"2014","journal-title":"Nat. Commun."},{"key":"ref17","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. 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Microbiol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"904","DOI":"10.3390\/nano13050904","article-title":"In vitro models of bacterial biofilms: innovative tools to improve understanding and treatment of infections","volume":"13","author":"Crivello","year":"2023","journal-title":"Nano"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.toxicon.2016.08.016","article-title":"Stigmurin and TsAP-2 from Tityus stigmurus scorpion venom: assessment of structure and therapeutic potential in experimental sepsis","volume":"121","author":"Daniele-Silva","year":"2016","journal-title":"Toxicon"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"170478","DOI":"10.1016\/j.peptides.2020.170478","article-title":"NMR three-dimensional structure of the cationic peptide Stigmurin from Tityus stigmurus scorpion venom: in vitro antioxidant and in vivo antibacterial and healing activity","volume":"137","author":"Daniele-Silva","year":"2021","journal-title":"Peptides"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"100191","DOI":"10.1016\/j.bioflm.2024.100191","article-title":"cmpX overexpression in Pseudomonas aeruginosa affects biofilm formation and cell morphology in response to shear stress","volume":"7","author":"David","year":"2024","journal-title":"Biofilm"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1016\/j.mib.2013.06.013","article-title":"Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies","volume":"16","author":"de la Fuente-N\u00fa\u00f1ez","year":"2013","journal-title":"Curr. 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Rep."},{"key":"ref27","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":"ref28","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/nrmicro.2016.94","article-title":"Biofilms: an emergent form of bacterial life","volume":"14","author":"Flemming","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"106245","DOI":"10.1016\/j.phrs.2022.106245","article-title":"In silico and in vitro structure-stability-function relationship of analog peptides of Stigmurin and its antibacterial and antibiofilm activities","volume":"181","author":"Furtado","year":"2022","journal-title":"Pharmacol. 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