{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:52:47Z","timestamp":1786117967429,"version":"build-2736575974"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Liaoning Provincial Science and Technology Program Joint Project","award":["2024-BSLH-270"],"award-info":[{"award-number":["2024-BSLH-270"]}]},{"name":"Liaoning Provincial Science and Technology Program Joint Project","award":["2025-BS-0524"],"award-info":[{"award-number":["2025-BS-0524"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M762161"],"award-info":[{"award-number":["2024M762161"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The synergistic interactions in multi-pathogen infections compromise wound healing and limit therapeutic efficacy. In this study, we designed and synthesized arginine-substituted derivatives of the antimicrobial peptide Mastoparan-C (MP-C). Among them, Arg\u00b2MP-C and Arg\n                      <jats:sup>4.11.12<\/jats:sup>\n                      MP-C exhibited potent, broad-spectrum activity against both\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      . Their enhanced antibacterial activity is associated with increased positive charge and optimized hydrophobicity. Mechanistically, both peptides employ a dual-target strategy, disrupting bacterial membranes and binding genomic DNA; Arg\u00b2MP-C acted most rapidly against the\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      envelope, while Arg\n                      <jats:sup>4.11.12<\/jats:sup>\n                      MP-C caused the strongest membrane damage to\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      . In a murine polymicrobial wound model, Arg\u00b2MP-C treatment nearly achieved complete wound closure by day 10, significantly reduced bacterial loads, and promoted tissue regeneration. This study demonstrates that arginine engineering can yield peptides with potent, multi-mechanistic action, identifying Arg\u00b2MP-C as a promising candidate for combating polymicrobial wound infections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Wounds infected with multiple bacterial species are notoriously difficult to treat, often leading to poor healing and limited effectiveness of existing therapies. In this study, we developed new antimicrobial peptides by introducing arginine substitutions into a natural peptide called Mastoparan-C. Two of our engineered peptides, Arg\u00b2MP-C and Arg\n                      <jats:sup>4.11.12<\/jats:sup>\n                      MP-C, showed potent activity against two common wound pathogens,\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      . These peptides work through a dual mechanism: disrupting bacterial membranes and binding to bacterial DNA. In a mouse model of mixed-infection wounds, treatment with Arg\u00b2MP-C led to nearly complete wound closure by day 10, drastically reduced bacterial counts, and promoted tissue repair. Our findings highlight arginine engineering as a promising strategy to create next\u2011generation antimicrobial agents that can effectively combat complex polymicrobial wound infections, addressing a critical unmet need in clinical wound care.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.04219-25","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:00:37Z","timestamp":1782738037000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Arginine-substituted Mastoparan-C derivatives combat dual bacterial pathogens:\n                    <i>in vitro<\/i>\n                    mechanistic insights and\n                    <i>in vivo<\/i>\n                    efficacy in polymicrobial 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