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To restore the efficacy of tetracyclines to Pm, we evaluated the synergistic antibacterial activity of doxycycline combined with metformin, an FDA-approved antidiabetic agent. Among several non-antibiotic adjuvant candidates, metformin exhibited the most potent in vitro synergy with doxycycline, especially against capsular serogroup A strain (PmA). The combination demonstrated minimal cytotoxicity and hemolysis in both mammalian and avian cells and effectively inhibited resistance development under doxycycline pressure. At 50 mg\/kg each, the combination of metformin and doxycycline significantly reduced mortality in mice and ducks acutely infected with PmA (from 100% to 60%), decreased pulmonary bacterial burdens, and alleviated tissue inflammation and damage. Mechanistic validation confirmed that metformin enhances membrane permeability in Pm without compromising membrane integrity, dissipates membrane potential, increases intracellular doxycycline accumulation, and downregulates the transcription of the tetracycline efflux gene tet(B). Morphological analyses further revealed pronounced membrane deformation and possible leakage of intracellular contents. These findings highlight metformin as a potent, low-toxicity tetracycline adjuvant with cross-species efficacy, offering a promising therapeutic approach for managing tetracycline-resistant Pm infections.<\/jats:p>","DOI":"10.3390\/microorganisms13081724","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T14:22:44Z","timestamp":1753280564000},"page":"1724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Metformin Enhances Doxycycline Efficacy Against Pasteurella multocida: Evidence from In Vitro, In Vivo, and Morphological Studies"],"prefix":"10.3390","volume":"13","author":[{"given":"Nansong","family":"Jiang","sequence":"first","affiliation":[{"name":"Research Center for Poultry Diseases, Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"},{"name":"Fujian Key Laboratory for Prevention and Control of Avian 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Microorganisms, 13.","DOI":"10.3390\/microorganisms13040938"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1093\/jac\/dkab462","article-title":"Defining the scope of the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet): A bottom-up and One Health approach","volume":"77","author":"Mader","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Parmanik, A., Das, S., Kar, B., Bose, A., Dwivedi, G.R., and Pandey, M.M. (2022). Current Treatment Strategies Against Multidrug-Resistant Bacteria: A Review. Curr. Microbiol., 79.","DOI":"10.1007\/s00284-022-03061-7"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, B., Fang, D., Lv, Q., Wang, Z., and Liu, Y. (2021). Targeted Therapeutic Strategies in the Battle Against Pathogenic Bacteria. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.673239"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s41579-019-0288-0","article-title":"The global preclinical antibacterial pipeline","volume":"18","author":"Theuretzbacher","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00018-009-0172-6","article-title":"The tetracycline resistome","volume":"67","author":"Thaker","year":"2010","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/med.21946","article-title":"Bacterial proton motive force as an unprecedented target to control antimicrobial resistance","volume":"43","author":"Yang","year":"2023","journal-title":"Med. Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1080\/1040841X.2023.2186215","article-title":"Antimicrobial peptides as promising antibiotic adjuvants to combat drug-resistant pathogens","volume":"50","author":"Chen","year":"2024","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Magnowska, Z., Jana, B., Brochmann, R.P., Hesketh, A., Lametsch, R., De Gobba, C., and Guardabassi, L. (2019). Carprofen-induced depletion of proton motive force reverses TetK-mediated doxycycline resistance in methicillin-resistant Staphylococcus pseudintermedius. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-54091-4"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Liu, Y., Tong, Z., Shi, J., Jia, Y., Deng, T., and Wang, Z. (2021). Reversion of antibiotic resistance in multidrug-resistant pathogens using non-antibiotic pharmaceutical benzydamine. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02854-z"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1902227","DOI":"10.1002\/advs.201902227","article-title":"Metformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria","volume":"7","author":"Liu","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/nchembio.559","article-title":"Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial efficacy","volume":"7","author":"Ejim","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xiao, X., Huan, Q., Huang, Y., Liu, Y., Li, R., Xu, X., and Wang, Z. (2022). Metformin Reverses tmexCD1-toprJ1- and tet(A)-Mediated High-Level Tigecycline Resistance in K. pneumoniae. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020162"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hossain, S., Rafi, R.H., Ripa, F.A., Khan, M.R.I., Hosen, M.E., Molla, M.K.I., Faruqe, M.O., Al-Bari, M.A.A., and Das, S. (2024). Modulating the antibacterial effect of the existing antibiotics along with repurposing drug metformin. Arch. Microbiol., 206.","DOI":"10.1007\/s00203-024-03917-5"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s44259-024-00047-2","article-title":"Drug combinations targeting antibiotic resistance","volume":"2","author":"Bognar","year":"2024","journal-title":"NPJ Antimicrob. Resist."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jiang, N., Chen, H., Wang, W., Liang, Q., Fu, Q., Liu, R., Fu, G., Wan, C., Huang, Y., and Cheng, L. (2025). Characterization of a Capsule-Deficient Pasteurella multocida Isolated from Cygnus melancoryphus: Genomic, Phenotypic, and Virulence Insights. Microorganisms, 13.","DOI":"10.3390\/microorganisms13051024"},{"key":"ref_23","unstructured":"Institute, C.L.S. (2024). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute (CLSI)."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41467-018-02875-z","article-title":"Overcoming mcr-1 mediated colistin resistance with colistin in combination with other antibiotics","volume":"9","author":"MacNair","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1802333","DOI":"10.1002\/advs.201802333","article-title":"Proanthocyanidin Interferes with Intrinsic Antibiotic Resistance Mechanisms of Gram-Negative Bacteria","volume":"6","author":"Maisuria","year":"2019","journal-title":"Adv. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1007\/s11427-021-2032-9","article-title":"Melatonin inhibits Gram-negative pathogens by targeting citrate synthase","volume":"65","author":"He","year":"2022","journal-title":"Sci. China Life Sci."},{"key":"ref_27","first-page":"83","article-title":"Metformin as a Potential Adjuvant Antimicrobial Agent Against Multidrug Resistant Bacteria","volume":"13","author":"Masadeh","year":"2021","journal-title":"Clin. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Guo, T., Sun, X., Yang, J., Yang, L., Li, M., Wang, Y., Jiao, H., and Li, G. (2022). Metformin reverse minocycline to inhibit minocycline-resistant Acinetobacter baumannii by destroy the outer membrane and enhance membrane potential in vitro. BMC Microbiol., 22.","DOI":"10.1186\/s12866-022-02629-4"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Arredondo, A., Alvarez, G., Nart, J., Mor, C., Blanc, V., and Leon, R. (2019). Detection and expression analysis of tet(B) in Streptococcus oralis. J. Oral Microbiol., 11.","DOI":"10.1080\/20002297.2019.1643204"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xu, G., Li, P., Xue, Z., Qi, Y., Li, X., Zhu, D., Ma, H., and Kong, L. (2024). RecA inhibitor epicatechin prolongs the development of fluoroquinolone resistance in Pasteurella multocida. Int. J. Biol. Macromol., 255.","DOI":"10.1016\/j.ijbiomac.2023.128026"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1126\/science.1238328","article-title":"Fe-S cluster biosynthesis controls uptake of aminoglycosides in a ROS-less death pathway","volume":"340","author":"Ezraty","year":"2013","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature10069","article-title":"Metabolite-enabled eradication of bacterial persisters by aminoglycosides","volume":"473","author":"Allison","year":"2011","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMoa012512","article-title":"Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin","volume":"346","author":"Knowler","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Liu, Y., Shi, J., Tong, Z., Jia, Y., Yang, K., and Wang, Z. (2020). Potent Broad-Spectrum Antibacterial Activity of Amphiphilic Peptides against Multidrug-Resistant Bacteria. Microorganisms, 8.","DOI":"10.3390\/microorganisms8091398"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s42000-019-00093-w","article-title":"Metformin and gut microbiota: Their interactions and their impact on diabetes","volume":"18","author":"Vallianou","year":"2019","journal-title":"Hormones"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hegazy, W.A.H., Khayat, M.T., Ibrahim, T.S., Nassar, M.S., Bakhrebah, M.A., Abdulaal, W.H., Alhakamy, N.A., and Bendary, M.M. (2020). Repurposing Anti-diabetic Drugs to Cripple Quorum Sensing in Pseudomonas aeruginosa. Microorganisms, 8.","DOI":"10.3390\/microorganisms8091285"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"128474","DOI":"10.1016\/j.jhazmat.2022.128474","article-title":"Emerging pollutant metformin in water promotes the development of multiple-antibiotic resistance in Escherichia coli via chromosome mutagenesis","volume":"430","author":"Wei","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"263ra159","DOI":"10.1126\/scitranslmed.3009885","article-title":"Metformin as adjunct antituberculosis therapy","volume":"6","author":"Singhal","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mediaas, S.D., Haug, M., Louet, C., Wahl, S.G.F., Gidon, A., and Flo, T.H. (2024). Metformin improves Mycobacterium avium infection by strengthening macrophage antimicrobial functions. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1463224"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1111\/cts.13051","article-title":"Effects of vancomycin-induced gut microbiome alteration on the pharmacodynamics of metformin in healthy male subjects","volume":"14","author":"Kim","year":"2021","journal-title":"Clin. Transl. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e011523","DOI":"10.1136\/bmjopen-2016-011523","article-title":"Metformin and other glucose-lowering drug initiation and rates of community-based antibiotic use and hospital-treated infections in patients with type 2 diabetes: A Danish nationwide population-based cohort study","volume":"6","author":"Mor","year":"2016","journal-title":"BMJ Open"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Shih, C.J., Wu, Y.L., Chao, P.W., Kuo, S.C., Yang, C.Y., Li, S.Y., Ou, S.M., and Chen, Y.T. (2015). Association between Use of Oral Anti-Diabetic Drugs and the Risk of Sepsis: A Nested Case-Control Study. Sci. Rep., 5.","DOI":"10.1038\/srep15260"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/8\/1724\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:14:42Z","timestamp":1760033682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/8\/1724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["microorganisms13081724"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13081724","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]}}}