{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:26:24Z","timestamp":1792430784750,"version":"4.5.0"},"reference-count":161,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Antibiotic pressure exerts profound effects on bacterial physiology, not limited to classical genetic resistance mechanisms. Increasing evidence highlights the ability of pathogens to undergo metabolic rewiring\u2014an adaptive, reversible reorganization of core metabolic pathways that promotes survival under antimicrobial stress. This review provides a comprehensive analysis of antibiotic-induced metabolic adaptations, encompassing glycolysis, the tricarboxylic acid cycle, fermentation, redox balance, amino acid catabolism, and membrane biosynthesis. We critically examine how diverse antibiotic classes\u2014including \u03b2-lactams, aminoglycosides, quinolones, glycopeptides, polymyxins, and antimetabolites\u2014interact with bacterial metabolism to induce tolerance and persistence, often preceding stable resistance mutations. In parallel, we explore the ecological and host-derived signals\u2014such as immunometabolites and quorum sensing\u2014that modulate these metabolic responses. Therapeutically, targeting metabolic pathways offers promising strategies to potentiate antibiotic efficacy, including enzyme inhibition, metabolic adjuvants, and precision-guided therapy based on pathogen metabolic profiling. By framing metabolic plasticity as a dynamic and evolutionarily relevant phenomenon, this review proposes a unifying model linking transient tolerance to stable resistance. Integrating metabolic rewiring into antimicrobial research, clinical diagnostics, and therapeutic design represents a necessary paradigm shift in combating bacterial persistence and resistance.<\/jats:p>","DOI":"10.3390\/ijms26125574","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T03:44:58Z","timestamp":1749613498000},"page":"5574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Metabolic Rewiring of Bacterial Pathogens in Response to Antibiotic Pressure\u2014A Molecular Perspective"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1239-7012","authenticated-orcid":false,"given":"Carlo","family":"Acierno","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, San Carlo Hospital, 85100 Potenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fannia","family":"Barletta","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, San Carlo Hospital, 85100 Potenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3320-3878","authenticated-orcid":false,"given":"Riccardo","family":"Nevola","sequence":"additional","affiliation":[{"name":"Liver Unit, AORN S. G. Moscati, \u201cA. Landolfi\u201d Hospital, 83029 Solofra, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Science \u201cVincenzo Tiberio\u201d, Universit\u00e0 degli Studi del Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9142-7848","authenticated-orcid":false,"given":"Ferdinando Carlo","family":"Sasso","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-4912","authenticated-orcid":false,"given":"Luigi Elio","family":"Adinolfi","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7761-7533","authenticated-orcid":false,"given":"Alfredo","family":"Caturano","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nrmicro3380","article-title":"Molecular mechanisms of antibiotic resistance","volume":"13","author":"Blair","year":"2015","journal-title":"Nat. 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