{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:13:01Z","timestamp":1792109581733,"version":"4.4.0"},"reference-count":56,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007492","name":"Baylor University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["enviromicro-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbial Biotechnology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Colorectal cancer (CRC) is a leading cause of cancer\u2010related mortality, with\n \n Fusobacterium nucleatum<\/jats:italic>\n <\/jats:styled-content>\n (\n \n F. nucleatum<\/jats:italic>\n <\/jats:styled-content>\n ) identified as a key contributor to its progression. This study explores a novel therapy that targets this pathogen by using a bioengineered probiotic that expresses guided antimicrobial peptides (gAMPs) to selectively inhibit\n \n F. nucleatum<\/jats:italic>\n <\/jats:styled-content>\n .\n Lactococcus lactis<\/jats:italic>\n MG1363 was engineered to express gAMPs derived from Ovispirin and Cathelin\u2010related peptide SCF, linked to a Statherin\u2010derived guide peptide that binds specifically to the\n \n F. nucleatum<\/jats:italic>\n <\/jats:styled-content>\n membrane porin FomA. The bacteria expressed the AMP\/gAMP under the induction of the PNisA promoter by nisin and secreted it via the extracellular secretion signal usp45. The resultant synthetic peptides and probiotics were assayed for antimicrobial activity against the targeted\n \n F. nucleatum<\/jats:italic>\n <\/jats:styled-content>\n and other non\u2010target bacteria. Biofilm inhibition and growth kinetic assays were performed with synthetic peptides in\u00a0vitro or the probiotic in co\u2010culture with a polymicrobial community. Statherin\u2010derived guide peptide enhanced the binding affinity to\n \n F. nucleatum<\/jats:italic>\n <\/jats:styled-content>\n , significantly increasing attachment compared to control peptides. In\u00a0vitro assays revealed that both unguided and guided AMPs effectively inhibited biofilm formation in\n \n F. nucleatum<\/jats:italic>\n <\/jats:styled-content>\n , with gAMPs showing reduced toxicity against non\u2010target bacteria. The gAMPs were more effective in modulating growth kinetics, exhibiting selective toxicity towards\n \n F. nucleatum<\/jats:italic>\n <\/jats:styled-content>\n at lower concentrations. Co\u2010culture experiments in a simulated human gut microbiome showed the gAMP probiotic maintained microbial diversity while effectively reducing\n \n F. nucleatum<\/jats:italic>\n <\/jats:styled-content>\n abundance. Quantitative PCR and 16S rRNA sequencing confirmed that gAMP treatment preserved the richness of the microbiota, contrasting with significant dysbiosis observed in control samples. These findings support the potential of engineered probiotics as a therapeutic approach that targets CRC\u2010associated\n \n F. nucleatum<\/jats:italic>\n <\/jats:styled-content>\n .\n <\/jats:p>","DOI":"10.1111\/1751-7915.70241","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T11:48:14Z","timestamp":1765367294000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Precision Antimicrobial Therapy Against\n Fusobacterium nucleatum<\/i>\n Using Bioengineered Probiotics Expressing Guided Antimicrobial Peptides (gAMPs)"],"prefix":"10.1111","volume":"18","author":[{"given":"Ankan","family":"Choudhury","sequence":"first","affiliation":[{"name":"Department of Biology, College of Arts & Sciences Baylor University Waco Texas USA"},{"name":"Department of Human Science and Design, Robbins College of Health and Human Sciences Baylor University Waco Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Scano","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Arts & Sciences Baylor University Waco Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Barton","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Arts & Sciences Baylor University Waco Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Kearney","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Arts & Sciences Baylor University Waco Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6855-8516","authenticated-orcid":false,"given":"K. 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