2026-10-13T21:52:29Z https://www.scidb.cn/oai

10.57760/sciencedb.46072 2026-08-18T14:47:31Z

2026-08-18 Icariside II suppresses Staphylococcus aureus biofilms and prevents virulence rebound through SarX and SarZ network modulation doi:10.57760/sciencedb.46072 en The rising clinical burden of multidrug-resistant Staphylococcus aureus infections urgently necessitates novel anti-virulence and anti-biofilm therapeutic strategies. While the natural flavonol glycoside Icariside II (Baohuoside I) is known to suppress staphylococcal virulence by targeting the SarZ regulator the exact mechanisms driving its profound biofilm-eradicating capacity remained a critical paradox. Here we identify the master regulator SarX as the primary and direct functional target responsible for the anti-biofilm efficacy of Icariside II. Through integrating multi-omics profiling targeted genetic ablations (ΔsarX and ΔsarZ) and biochemical interaction assays we demonstrate that Icariside II physically binds to SarX and neutralizes its transcriptional activation of the icaADBC operon effectively dismantling the protective extracellular matrix. Most importantly, the genetic loss of sarX triggers a systemic network rewiring that massively upregulates key hemolysins such as gamma-hemolysin (HlgCB), Staphopain B, and LukDv alongside the KdpCDE stress adaptation transport system. Functionally, this genomic rewiring drives a rapid and massive hemolytic storm that is resistant to targeted intervention. Strikingly the dual-action pharmacological profile of Icariside II overcomes this evolutionary bottleneck. By concurrently blocking the SarZ node within an undisrupted regulatory network the drug suppresses the virulence storm and forces the pathogen into a vulnerable non-invasive state. Ultimately this study delineates an unprecedented dual-target paradigm where Icariside II acts as a systemic network disruptor. This targeted interference strips the pathogen of its defenses by blocking both matrix assembly and toxigenic responses establishing a comprehensive strategy for treating multidrug-resistant Gram-positive infections.  Staphylococcus aureus; Icariside II; ica; biofilm; SarX; SarZ Zewen Wen PUBLIC https://creativecommons.org/licenses/by/4.0/ dataset Science Data Bank