Phloretin reduces cell injury and inflammation mediated by Staphylococcus aureus via targeting sortase B and the molecular mechanism
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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.
KeywordsStaphylococcus aureus Phloretin Sortase B Cytotoxicity Adhesion Inflammation Molecular simulations
X.D.N. and J.F.W. conceived and designed the experiments. G.Z.W. and Y.W.G. performed the experiments. H.S.W. and Y.W.G contributed reagents/materials/analysis tools. X.D.N., J.F.W., and G.Z.W. wrote the paper.
This work was supported by the National Nature Science Foundation of China [Grant No. 31402251, 31602109 to H.S.W] and the National Nature Science Foundation of China [Grant No. 31572566 to X.D.N].
Compliance with ethical standards
This article does not contain any studies with human participants or animals performed by any of the authors.
Conflict of interest
The authors declare that they have no conflicts of interest.
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