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Compounds from Cyclocarya paliurus leaves inhibit binary division of methicillin-resistant Staphylococcus aureus by

Wenlong Chen1, Shuixian Zhang1, Chunxu Huang1

  • 1Center for Infectious Disease and Vaccine Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.

Frontiers in Microbiology
|July 3, 2025
PubMed

Insights

Novel compounds from Cyclocarya paliurus leaves target methicillin-resistant Staphylococcus aureus (MRSA) by disrupting cell division protein FtsZ. Asiatic acid shows promise as a bactericidal anti-MRSA lead compound.

Area of Science:

  • Microbiology
  • Pharmacology
  • Medicinal Chemistry

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health threat, demanding new therapeutic strategies.
  • Previous research indicated that an extract from Cyclocarya paliurus leaves (ECPL) inhibits MRSA by targeting the FtsZ cell division protein.

Purpose of the Study:

  • To isolate and characterize compounds from ECPL with anti-MRSA activity.
  • To elucidate the mechanism of action of these compounds on MRSA cell division.
  • To evaluate the therapeutic potential of the most promising compound in a preclinical model.

Main Methods:

  • Isolation of compounds from ECPL using bioactivity-guided fractionation.
  • Antibacterial activity assays, time-kill kinetics, and cell elongation measurements.
  • Surface Plasmon Resonance (SPR) analysis and molecular docking to study FtsZ interactions.
  • In vivo efficacy study using a murine skin infection model.

Main Results:

  • Three compounds, asiatic acid (AA), maslinic acid (MA), and ursolic acid (UA), were isolated and showed antibacterial activity against MRSA.
  • AA and MA demonstrated bactericidal effects, while UA was bacteriostatic, all inducing cell elongation.
  • Compounds differentially modulated FtsZ dynamics: AA promoted polymerization, while MA and UA inhibited it, with direct binding to FtsZ.
  • AA exhibited a distinct binding mode to FtsZ compared to MA and UA.
  • In vivo, AA significantly reduced bacterial burden and accelerated wound healing in a murine skin infection model.

Conclusions:

  • Asiatic acid, maslinic acid, and ursolic acid are direct FtsZ-targeting agents against MRSA.
  • Asiatic acid, with its unique FtsZ modulation and bactericidal activity, represents a promising lead compound for developing new anti-MRSA therapies.
  • Targeting the bacterial divisome offers a viable strategy for combating MRSA infections.
Keywords:
FtsZ dynamicsantimicrobial resistancecell divisionfilamenting temperature-sensitive mutant Zmethicillin-resistant Staphylococcus aureus

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