{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T05:00:05Z","timestamp":1776488405205,"version":"3.51.2"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFD1800100"],"award-info":[{"award-number":["2023YFD1800100"]}]},{"DOI":"10.13039\/501100012421","name":"Agricultural Science and Technology Innovation Program","doi-asserted-by":"crossref","award":["IFR\u201306"],"award-info":[{"award-number":["IFR\u201306"]}],"id":[{"id":"10.13039\/501100012421","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Pasteurella multocida (P. multocida) is not only the core pathogen of bovine respiratory disease (BRDC) but also a significant zoonotic agent, posing a dual threat to global animal husbandry and public health. This study utilized untargeted metabolomics to systematically dissect the metabolic regulatory network of P. multocida in response to tylosin within a One Health framework. The results revealed significant \u201cdefense\u2013growth\u201d metabolic reprogramming: activation of amino sugar and nucleotide sugar pathways (e.g., CDP-glucose) indicated cell wall remodeling, while directional shifts in the phenylalanine\u2013tyrosine network directed flux toward defensive secondary metabolites. Concurrently, amino acid disorders and the overactivation of the ABC transporter system exacerbated an internal energy crisis, characterized by a shift from respiration to glycolysis, ATP depletion, and ROS accumulation. SEM observations confirmed membrane integrity disruption and cytoplasmic leakage. Crucially, this metabolic stress and the transition into a \u201cpersister-like\u201d dormant state are closely linked to the adaptive expression of antimicrobial resistance (AMR) genes. Under the selective pressure of tylosin, these metabolic perturbations may facilitate the emergence and horizontal transfer of resistance determinants, which can circulate through the animal\u2013human\u2013environment interface. By revealing the metabolic physiological basis of tylosin\u2019s action and its role in inducing bacterial tolerance, this study provides critical theoretical insights for antimicrobial stewardship, aiming to mitigate the risk of AMR transmission and preserve the efficacy of macrolides for both veterinary and human medicine.<\/jats:p>","DOI":"10.3390\/vetsci13040386","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:35:42Z","timestamp":1776339342000},"page":"386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Study on the Non-Target Metabolomics Effects of Tylosin on Pasteurella multocida"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1310-2588","authenticated-orcid":false,"given":"Ting","family":"Zhang","sequence":"first","affiliation":[{"name":"National Feed Drug Reference Laboratories, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhao","family":"Xiang","sequence":"additional","affiliation":[{"name":"National Feed Drug Reference Laboratories, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaoxin","family":"Tang","sequence":"additional","affiliation":[{"name":"National Feed Drug Reference Laboratories, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiubo","family":"Li","sequence":"additional","affiliation":[{"name":"National Feed Drug Reference Laboratories, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China"},{"name":"Key Laboratory of Animal Antimicrobial Resistance Surveillance, Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9779-7321","authenticated-orcid":false,"given":"Yiming","family":"Liu","sequence":"additional","affiliation":[{"name":"National Feed Drug Reference Laboratories, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China"},{"name":"Key Laboratory of Animal Antimicrobial Resistance Surveillance, Ministry of Agriculture and Rural Affairs, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1017\/S1466252307001399","article-title":"Pasteurella multocida and bovine respiratory disease","volume":"8","author":"Dabo","year":"2007","journal-title":"Anim. 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