{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T08:32:31Z","timestamp":1786523551853,"version":"build-2736575974"},"reference-count":74,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The oral cavity represents an extremely complex and dynamic microbial ecosystem capable of rapidly adapting to antimicrobial stress. These characteristics make it a promising environment for the identification of novel bioactive molecules with therapeutic potential. At the same time, the increasing prevalence of resistant pathogens in dental and oral-maxillofacial infections highlights the limitations of current therapeutic strategies and the urgent need for new effective antibacterial agents. This review examines the central role of advanced analytical techniques, with particular emphasis on mass spectrometry, in the discovery and characterization of bioactive metabolites and biomarkers relevant to future antibacterial discovery and to the understanding of biological responses to pathogens or therapeutic interventions. It discusses how the integration of metabolomics approaches, imaging mass spectrometry, and bioinformatics platforms is transforming the antibacterial discovery process by accelerating the identification of active compounds and improving the understanding of microbial interactions within the oral cavity. Overall, this work provides an up-to-date overview of current knowledge regarding the oral microbiome as a source of bioactive molecules and biomarkers. It highlights how emerging analytical technologies are opening new perspectives for the development of innovative therapeutic strategies against resistant oral infections.<\/jats:p>","DOI":"10.3390\/molecules31162804","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:57:26Z","timestamp":1786521446000},"page":"2804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Cavity Antibacterial Discovery Pipeline Driven by Advanced Analytical Techniques"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-9104","authenticated-orcid":false,"given":"Antonella Maria","family":"Aresta","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment, University of Bari, Via Edoardo Orabona, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada Stefania","family":"Signorile","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, via Napoli 121, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Clemente","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, via Napoli 121, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"De Vietro","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment, University of Bari, Via Edoardo Orabona, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0588-3688","authenticated-orcid":false,"given":"Carlo","family":"Zambonin","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment, University of Bari, Via Edoardo Orabona, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cell.2020.02.056","article-title":"The science of antibiotic discovery","volume":"181","author":"Lewis","year":"2020","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/s41570-021-00313-1","article-title":"Towards the sustainable discovery and development of new antibiotics","volume":"5","author":"Miethke","year":"2021","journal-title":"Nat. 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