AI Article Synopsis

  • The rise of antibiotic-resistant bacteria like MRSA has led researchers to explore anti-virulence treatments, moving away from traditional antibiotics.
  • This study found that daphnetin can effectively disrupt MRSA's ability to adhere and invade cells by targeting the enzyme Sortase A (SrtA) and the toxin α-hemolysin (Hla).
  • Daphnetin not only inhibited key MRSA processes such as biofilm formation and hemolysis but also showed potential in protecting against MRSA-induced pneumonia in vivo, making it a promising candidate for treating bacterial infections.

Article Abstract

The increasing prevalence of antibiotic-resistant bacteria, represented by Methicillin-resistant Staphylococcus aureus (MRSA), has necessitated a shift towards anti-virulence strategies in treatment approaches. This research demonstrated that daphnetin effectively disrupted MRSA virulence by targeting Sortase A (SrtA), an enzyme in Staphylococcus aureus (S. aureus) responsible for adhesion and invasion, as well as the toxin α-hemolysin (Hla) that leads to cell lysis. Utilizing Fluorescence Resonance Energy Transfer, daphnetin showed direct inhibitory effect on SrtA activity, with an IC of 25.98 μg/mL. Additionally, daphnetin hindered various SrtA-mediated processes in S. aureus, such as fibronectin adherence, A549 cell invasion, biofilm formation, and bacterial motility. Daphnetin inhibited S. aureus-induced hemolysis and reduced Hla expression as confirmed by Western blot analysis. Molecular docking studies identified specific binding sites of daphnetin with SrtA, highlighting key amino acid residues like GLU-77, TYR-75, and LYS-145, with a docking score of -7.139 kcal/mol. Besides that, daphnetin exhibited a protective effect on MRSA-induced pneumonia in vivo. In summary, daphnetin, a natural compound, effectively inhibited SrtA and Hla activities, attenuating MRSA virulence and showcasing potential for treating bacterial infections.

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Source
http://dx.doi.org/10.1016/j.biochi.2024.10.010DOI Listing

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