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

Abstract

Our outcomes demonstrated vancomycin resistance in 13.7% of <i>Staphylococcus aureus</i> (<i>S. aureus</i>) strains categorized as VRSA. Notably, strong biofilm formation was observed in 69.2% of VRSA strains that were all positive for <i>icaA</i> gene. All strong biofilm-producing VRSA strains harbored a minimum of two virulence genes comprising <i>clfA</i> and <i>icaA</i> with 44.4% of them possessing all five virulence genes (<i>icaA</i>, <i>tst</i>, <i>clfA</i>, <i>hla</i>, and <i>pvl</i>), and 88.9% being multi-virulent. The study findings affirmed excellent <i>in vitro</i> 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 <i>agr</i> genes in both <i>in vitro</i> and <i>in vivo</i> 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.