{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T06:01:11Z","timestamp":1781157671957,"version":"3.54.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"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>Introduction<\/jats:title>\n                    <jats:p>\n                      The growth-inhibiting effect of the peptide Uy234, present in the venom of the scorpion\n                      <jats:italic>Urodacus yaschenkoi<\/jats:italic>\n                      , has been investigated in two bacterial pathogens:\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      ATCC 25923 and\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                      AE12, the latter being a multidrug-resistant clinical isolate. With the aim of determining the possible role of specific residues in the bioactivity of this peptide, we studied a proline residue at position 9 and the C-terminal amidation of this peptide.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two inactivated variants were analyzed: Uy234-C, a non-amidated peptide, and Uy234-A, a P9A mutant. In addition to quantifying in detail the minimum inhibitory and bactericidal concentrations for each microorganism, membrane-damaging effects were assessed through bacterial cell viability assays with SYTO9\/PI fluorophores. In addition, AFM, electroforming, and GUV microaspiration were used to determine the effects of each peptide in terms of permeabilization. Molecular dynamics (MD) simulations were also performed for the wild-type peptide and its P9A mutant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Only the native peptide Uy234 showed bacteriostatic and bactericidal activity, whereas the P9A mutant and non-amidated variant lost antimicrobial activity, demonstrating the essential role of the Pro-9 residue and C-terminal amidation in Uy234 bioactivity against both pathogens. SYTO9\/PI assays in\n                      <jats:italic>S. aureus<\/jats:italic>\n                      infection showed membrane damage only with native Uy234, while AFM and GUV studies revealed membrane thinning, lateral expansion, and dose-dependent permeabilization of lipid bilayers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our study provides clear evidence of a damaging effect on the membrane associated with the bioactivity of Uy234. This bioactivity is directly associated with the presence of residue P9 and the presence of C-terminal carboxyamidation. The mutant peptide P9A is unable to permeabilize GUVs, which is consistent with the persistence of a greater degree of structural order, according to MD simulations in the aqueous phase. This study provides a framework for the rational design of bactericidal peptides targeting multidrug-resistant bacteria.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1830314","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:46:59Z","timestamp":1781156819000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural determinants of the scorpion venom peptide Uy234 govern bactericidal activity and membrane-disruptive properties"],"prefix":"10.3389","volume":"17","author":[{"given":"Ana Karen","family":"Villa-Merlan","sequence":"first","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular y Biotecnolog\u00eda, Centro de Investigaciones en Ciencias Microbiol\u00f3gicas, Instituto de Ciencias, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla","place":["Puebla, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mescola","sequence":"additional","affiliation":[{"name":"CNR-Nanoscience Institute-S3","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Alejandro","family":"Fong-Coronado","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular y Biotecnolog\u00eda, Centro de Investigaciones en Ciencias Microbiol\u00f3gicas, Instituto de Ciencias, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla","place":["Puebla, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor Rivelino","family":"Ju\u00e1rez Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Direcci\u00f3n de Posgrado en Ciencias en Biotecnolog\u00eda, Universidad Polit\u00e9cnica del Estado de Morelos","place":["Jiutepec, Mexico"]},{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Cuernavaca, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Fern\u00e1ndez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Laboratorio de Microbiolog\u00eda, Unidad de Investigaci\u00f3n y Desarrollo en Alimentos (UNIDA), Instituto Tecnol\u00f3gico de Veracruz, Tecnol\u00f3gico Nacional de M\u00e9xico","place":["Veracruz, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Alessandrini","sequence":"additional","affiliation":[{"name":"CNR-Nanoscience Institute-S3","place":["Modena, Italy"]},{"name":"Department of Physics, Informatics and Mathematics, University of Modena and Reggio Emilia","place":["Modena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Balleza","sequence":"additional","affiliation":[{"name":"Laboratorio de Microbiolog\u00eda, Unidad de Investigaci\u00f3n y Desarrollo en Alimentos (UNIDA), Instituto Tecnol\u00f3gico de Veracruz, Tecnol\u00f3gico Nacional de M\u00e9xico","place":["Veracruz, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Quintero-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular y Biotecnolog\u00eda, Centro de Investigaciones en Ciencias Microbiol\u00f3gicas, Instituto de Ciencias, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla","place":["Puebla, Mexico"]},{"name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI)","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers.","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1016\/j.micron.2012.03.013","article-title":"Nanoscale mechanical properties of lipid bilayers and their relevance in biomembrane organization and function.","volume":"43","author":"Alessandrini","year":"2012","journal-title":"Micron"},{"key":"B3","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.peptides.2013.10.021","article-title":"Scorpion venom peptides with no disulfide bridges: A review.","volume":"51","author":"Almaaytah","year":"2014","journal-title":"Peptides"},{"key":"B4","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/B978-0-12-185255-9.50021-3","article-title":"Small injections of axonally transported fluorescent tracers.","volume":"3","author":"Almheid","year":"1990","journal-title":"Methods Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1039\/dc9868100303","article-title":"Faraday Discuss.","volume":"81","author":"Angelova","year":"1986","journal-title":"Chem. 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