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Sortase B (SrtB) is a vital virulence factor that plays a critical role in Staphylococcus aureus (S. aureus) infections, indicating that it could be a latent target for S. aureus infections. In this study, phloretin, a natural compound that primarily exists in the pericarp and velamen of apples and pears, shows little anti-S. aureus activity, but significantly inhibited SrtB activity in vitro. The results of lactate dehydrogenase release and live/dead cell assays suggested that phloretin reduced human alveolar epithelial cell damage caused by S. aureus. Additionally, an adhesion assay confirmed that phloretin lowered the colony count of S. aureus in human alveolar cells. Phloretin treatment significantly attenuated the inflammatory response in macrophage cells (J774) co-cultured with S. aureus as determined by an enzyme-linked immune-sorbent assay. Furthermore, the results of molecular dynamics simulation, site-directed mutagenesis, and fluorescence spectroscopy quenching indicated that phloretin was directly located in the active pocket of SrtB and blocked substrate binding, leading to the loss of SrtB activity. These results indicate that phloretin is a possible candidate for treatment of S. aureus infections. [ABSTRACT FROM AUTHOR]

The images of cells under microscope in Figure 2 and Figure S2 were misused from Wang G et al. Front Cell Infect Microbiol. 2018 Nov 30;8:418. These images were generated in the same set of assays. [ABSTRACT FROM AUTHOR]