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Aims Coagulase (Coa), a crucial virulence factor of Staphylococcus aureus (S. aureus), is considered a vital target for anti-virulence strategies. The research aimed to discover a natural compound capable of inhibiting S. aureus infection by targeting the virulence factor Coa. Methods and results The study showed that sinensetin at a concentration of 128 μg mL−1 effectively inhibited both Coa-induced coagulation and biofilm formation in S. aureus. However, western blot results indicated that sinensetin did not impact the expression of Coa protein, suggesting that sinensetin may directly target Coa to counteract the virulence of S. aureus. Thermal shift assay results demonstrated that sinensetin enhanced the thermal stability of Coa, supporting the theory of direct binding. Molecular docking and point mutation experiments identified two key binding sites for sinensetin to Coa as R73A-Coa and R204A-Coa. In vivo studies on mice revealed that sinensetin not only reduced lung tissue damage caused by S. aureus infection, but also decreased inflammatory factors in the lung lavage fluid. Furthermore, combining sinensetin with oxacillin improved the survival rates of the Galleria mellonella and mice. Conclusions Sinensetin is a promising natural compound that acts as a direct inhibitor of Coa against S. aureus infections. [ABSTRACT FROM AUTHOR]

The accurate assessment of hydraulic transmissivity in rock fractures filled with particles is not only a scientific challenge but also a critical need for various industrial applications. However, the intricate dynamics of particle erosion and pore clogging that govern transmissivity evolution remain largely unexplored. In this study, we experimentally examine the fluid‐driven particle migration behavior in filled fractures and its consequent impact on fracture transmissivity under various hydraulic gradients, normal stresses, and fracture apertures. We find that escalating hydraulic gradients not only intensify particle erosion through amplified fluid drag forces and hydro‐mechanical coupling effects but also lead to an increase in the size of migrating particles, thereby augmenting pore clogging. The dynamics of erosion and clogging define four distinct migration phases within the filled fractures. Variations in normal stress and initial fracture aperture significantly alter the particle arrangement and the soil structure stability within the fractures, thereby modulating the progress of particle migration in response to hydraulic gradients. The pattern of particle migration in filled fractures dictates the development of the internal pore structure and normal deformation, ultimately affecting fracture transmissivity. We propose an empirical expression to encapsulate the comprehensive evolution of fracture transmissivity across different particle migration patterns. Our research advances the understanding of fluid‐driven particle migration within filled fractures and provides a practical tool for the precise determination of hydraulic properties of fractured rocks amidst complex geological settings. Plain Language Summary: Filled fractures in rock masses, serving as dominant flow channels and potential failure planes, are typically perceived to exhibit constant hydraulic transmissivity. However, this perspective oversimplifies the dynamic nature of filled fractures, where fluid flow can greatly change the hydraulic characteristics by either eroding or accumulating the internal particles. Understanding how these filling particles respond to water flow and affect fracture transmissivity is vital for many geological processes and human activities. Here, we experimentally uncover four distinct phases of particle migration within a filled fracture, instigated by the dynamics of erosion and clogging under elevated hydraulic gradients. Variations in normal stress and fracture aperture significantly influence the particle arrangement and the soil structure stability within fractures, thereby affecting particle migration characteristics across phases. On this basis, we delve into how the patterns of particle migration impact the geometric structure of the filled fracture and, thus, the fracture transmissivity. Finally, we quantitatively portray the evolution in fracture transmissivity across various particle migration scenarios using an empirical model. Our findings enhance the understanding of fluid‐driven particle migration in filled fractures and provide a path forward for accurately assessing the hydraulic properties of fractured rocks in complex geological environments. Key Points: Erosion and clogging dynamics, modulated by hydraulic gradients, define four particle migration phases in stressed‐filled fracturesParticle migration patterns dictate pore structure and normal deformation, impacting fracture transmissivityAn empirical model encapsulates fracture transmissivity evolution across different particle migration patterns [ABSTRACT FROM AUTHOR]