{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:37:41Z","timestamp":1791290261892,"version":"4.3.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T00:00:00Z","timestamp":1705017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>As a growing direction, nano-based therapy has become a successful paradigm used to address the phytogenic delivery-related problems in overcoming multivirulent vancomycin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (VRSA) infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Hence, our aim was to develop and assess a novel nanocarrier system (mesoporous silica nanoparticles, MPS-NPs) for free berberine (Free-BR) as an antimicrobial alkaloid against strong biofilm-producing and multi-virulent VRSA strains using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Our outcomes demonstrated vancomycin resistance in 13.7% of <jats:italic>Staphylococcus aureus<\/jats:italic> (<jats:italic>S. aureus<\/jats:italic>) strains categorized as VRSA. Notably, strong biofilm formation was observed in 69.2% of VRSA strains that were all positive for <jats:italic>icaA<\/jats:italic> gene. All strong biofilm-producing VRSA strains harbored a minimum of two virulence genes comprising <jats:italic>clfA<\/jats:italic> and <jats:italic>icaA<\/jats:italic> with 44.4% of them possessing all five virulence genes (<jats:italic>icaA<\/jats:italic>, <jats:italic>tst<\/jats:italic>, <jats:italic>clfA<\/jats:italic>, <jats:italic>hla<\/jats:italic>, and <jats:italic>pvl<\/jats:italic>), and 88.9% being multi-virulent. The study findings affirmed excellent <jats:italic>in vitro<\/jats:italic> antimicrobial and antibiofilm properties of BR-loaded MPS-NPs. Real-time quantitative reverse transcription PCR (qRT-PCR) assay displayed the downregulating role of BR-loaded MPS-NPs on strong biofilm-producing and multi-virulent VRSA strains virulence and <jats:italic>agr<\/jats:italic> genes in both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> mice models. Additionally, BR-loaded MPS-NPs supplementation has a promising role in attenuating the upregulated expression of pro-inflammatory cytokines\u2019 genes in VRSA-infected mice with attenuation in pro-apoptotic genes expression resulting in reduced VRSA-induced apoptosis. In essence, the current study recommends the future scope of using BR-loaded MPS-NPs as auspicious alternatives for antimicrobials with tremendous antimicrobial, antibiofilm, anti-quorum sensing (QS), and anti-virulence effectiveness against problematic strong biofilm-producing and multi-virulent VRSA-associated infections.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1287426","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T04:34:02Z","timestamp":1705034042000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Tackling strong biofilm and multi-virulent vancomycin-resistant Staphylococcus aureus via natural alkaloid-based porous nanoparticles: perspective towards near future eradication"],"prefix":"10.3389","volume":"13","author":[{"given":"Marwa I.","family":"Abd El-Hamid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara T.","family":"Elazab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa M.","family":"Gad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Shalaby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa M.","family":"El-Neshwy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Abdulrahman","family":"Alshahrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Saif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem M.","family":"Algendy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"AlHarbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayez M.","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afaf","family":"Alharthi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman A. 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