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Prot."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Enterococcus faecalis<\/jats:italic>\n                    (\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    ) is an opportunistic pathogen associated with severe infections, particularly in hospital settings. Increasing antibiotic resistance and diverse virulence factors highlights the urgent need for innovative, effective therapeutic approaches. In this study, a lactoferrin\u2013Bismuth Nanoform (LF-Bi-NF) was synthesized and comprehensively characterized using UV\u2013visible spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) mapping, dynamic light scattering (DLS), and Fourier-transform infrared (FTIR) spectroscopy. However, gamma radiation negatively impacted the stability of LF-Bi-NF. The LF-Bi-NF was evaluated against pathogenic\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    isolates through in vitro assays, in addition to in vivo investigations\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    infected mice. The LF-Bi-NF exhibited antibacterial activity, with inhibition zones of 20.0\u2009\u00b1\u20090.10, 21.0\u2009\u00b1\u20090.15, 18.0\u2009\u00b1\u20090.25, and 15.0\u2009\u00b1\u20090.31\u00a0mm against\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    _1,\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    _2,\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    _3, and\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    ATCC 29212, respectively. While both lactoferrin and bismuth salts alone exhibited no detectable activity. The LF-Bi-NF demonstrated minimum inhibitory concentrations (MICs) of 3.125, 1.56, 6.25, and 12.5\u00a0\u00b5g\/mL and minimum bactericidal concentrations (MBCs) of 12.50, 3.125, 25, and 25\u00a0\u00b5g\/mL against the respective isolates, along with inhibition of biofilm formation at sub-MIC levels. Mechanistic investigations indicated disruption of cell wall integrity, increased membrane permeability, and protein leakage, particularly in the strong biofilm-forming isolate\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    _2. Additionally, gene expression analysis showed that the antibiotic resistance-associated genes\n                    <jats:italic>norA<\/jats:italic>\n                    and\n                    <jats:italic>ermC<\/jats:italic>\n                    and the virulence-associated gene\n                    <jats:italic>EF3314<\/jats:italic>\n                    were downregulated by 64%, 59%, and 87%, respectively. In vivo studies demonstrated that LF-Bi-NF treatment promoted recovery in infected mice, improved immunological biomarkers (IL-12, IL-10, MPO, and IFN-\u03b3), and significantly reduced bacterial burden in the bloodstream to undetectable levels within four days. In conclusion, LF-Bi-NF represents a promising nano-therapeutic candidate for the treatment of\n                    <jats:italic>E. faecalis<\/jats:italic>\n                    infections, exhibiting strong antibacterial, anti-biofilm, anti-virulence, and immunomodulatory properties.\n                  <\/jats:p>","DOI":"10.1007\/s12602-026-11078-8","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T10:30:42Z","timestamp":1781001042000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Pathogenic Infection and Virulence Genes of Enterococcus Faecalis Using Lactoferrin Bismuth Nano-form"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1784-101X","authenticated-orcid":false,"given":"Farag M.","family":"Mosallam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia A.","family":"Elzahaby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman A.","family":"Helmy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa M.","family":"Helal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana Mohamed","family":"Elshimy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"11078_CR1","unstructured":"Caliman-Sturdza OA (2024) Enteroccocus and Endocarditis. 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