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Therefore, the current study aimed to investigate the effects of thyme-synthesized silver nanoparticles (thyme-AgNPs) on modulating the immunosuppressive, oxidative stress, and histopathological changes induced by multidrug-resistant <jats:italic>Enterococcus faecalis<\/jats:italic> (MDR <jats:italic>E. faecalis<\/jats:italic>) infection in <jats:italic>Oreochromis niloticus<\/jats:italic> (Nile tilapia)<jats:italic>.<\/jats:italic> The antibiotic susceptibility profiling of the isolated <jats:italic>E. faecalis<\/jats:italic> (PQ084785) revealed resistance to multiple antibiotic classes. The in vitro bactericidal efficacy of thyme-AgNPs was confirmed, with minimum bactericidal concentrations (MBC) and minimum inhibitory concentrations (MIC) of 62.5\u00a0\u00b5g\/mL and 31.5\u00a0\u00b5g\/mL, respectively. In vivo, the 96-h median lethal concentration (LC<jats:sub>50<\/jats:sub>) of thyme-AgNPs was determined to be 1\u00a0mg\/L. Meanwhile, eighty <jats:italic>O. niloticus<\/jats:italic> (30.00\u2009\u00b1\u20095.00\u00a0g) were categorized into four groups in duplicate: group I was the negative control group, group II was intraperitoneally injected with MDR <jats:italic>E. faecalis<\/jats:italic> (0.2\u00a0mL of 0.79\u2009\u00d7\u200910<jats:sup>8<\/jats:sup>\u00a0CFU\/mL), group III was exposed to the sublethal dose of thyme-AgNPs in water (0.1\u00a0mg\/L), and group IV was challenged with the <jats:italic>E. faecalis<\/jats:italic> and exposed to thyme-AgNPs simultaneously for 15\u00a0days. Results outlined that <jats:italic>E. faecalis<\/jats:italic> induced clinical abnormalities<jats:italic>,<\/jats:italic> reduced immunoglobulin M levels, elevated oxidant indicators (malondialdehyde), decreased antioxidant capacity (reduced glutathione content, catalase, and superoxide dismutase), and significantly upregulated immune gene expression (tumor necrosis factor-\u03b1 and interleukin-1\u03b2) with marked histopathological and histochemical alterations in gill and liver tissues. Interestingly, the thyme-AgNPs intervention resulted in a noticeable improvement in all measured biomarkers as well as histopathological regeneration. Overall, thyme-AgNPs are a recent antibacterial tool against immune-oxidant\/antioxidant and histopathological changes triggered by MDR <jats:italic>E. faecalis<\/jats:italic> infection.<\/jats:p>","DOI":"10.1007\/s10695-025-01560-5","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T08:50:44Z","timestamp":1755247844000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Thyme-synthesized silver nanoparticles mitigate immunosuppression, oxidative damage, and histopathological alterations induced by multidrug-resistant Enterococcus faecalis in Oreochromis niloticus: in vitro and in vivo assays"],"prefix":"10.1007","volume":"51","author":[{"given":"Dalia A.","family":"Abdel-moneam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan","family":"S.\u00a0Khalefa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha M.","family":"Rashad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada E.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine H.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Ragab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama A.","family":"Fouad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramadan A.","family":"Geioushy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahr B.","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"1560_CR1","doi-asserted-by":"publisher","unstructured":"A\u2019yunin Q, Budianto Andayani S, Yuwanita R (2020) Histopathological analysis of Pangasius sp. infected by Edwardsiella tarda causes Edwardsiellosis disease. 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