AUTHOR=Abd El-Hamid Marwa I. , Ibrahim Doaa , Elazab Sara T. , Gad Wafaa M. , Shalaby Marwa , El-Neshwy Wafaa M. , Alshahrani Mohammed Abdulrahman , Saif Ahmed , Algendy Reem M. , AlHarbi Maha , Saleh Fayez M. , Alharthi Afaf , Mohamed Eman A. A. 

TITLE=Tackling strong biofilm and multi-virulent vancomycin-resistant Staphylococcus aureus via natural alkaloid-based porous nanoparticles: perspective towards near future eradication

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1287426

DOI=10.3389/fcimb.2023.1287426

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><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 <italic>Staphylococcus aureus</italic> (VRSA) infection.</p></sec><sec><title>Methods</title><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 <italic>in vitro</italic> and <italic>in vivo</italic> mouse model.</p></sec><sec><title>Results and discussion</title><p>Our outcomes demonstrated vancomycin resistance in 13.7% of <italic>Staphylococcus aureus</italic> (<italic>S. aureus</italic>) strains categorized as VRSA. Notably, strong biofilm formation was observed in 69.2% of VRSA strains that were all positive for <italic>icaA</italic> gene. All strong biofilm-producing VRSA strains harbored a minimum of two virulence genes comprising <italic>clfA</italic> and <italic>icaA</italic> with 44.4% of them possessing all five virulence genes (<italic>icaA</italic>, <italic>tst</italic>, <italic>clfA</italic>, <italic>hla</italic>, and <italic>pvl</italic>), and 88.9% being multi-virulent. The study findings affirmed excellent <italic>in vitro</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 <italic>agr</italic> genes in both <italic>in vitro</italic> and <italic>in vivo</italic> mice models. Additionally, BR-loaded MPS-NPs supplementation has a promising role in attenuating the upregulated expression of pro-inflammatory cytokines’ 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.</p></sec>