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Pyrimirhodomyrtone inhibits Staphylococcus aureus by affecting the activity of NagA

Huan Zeng1, Minjing Cheng2, Jingyi Liu3

  • 1Center for Bioactive Natural Molecules and Innovative Drugs Research, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 511443, Guangdong, China; Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.

Biochemical Pharmacology
|February 13, 2023
PubMed

Insights

Pyrimrhodomyrtone (PRM) shows antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA). This natural product derivative inhibits the NagA enzyme and disrupts the bacterial cell membrane, offering a new avenue for anti-MRSA drug development.

Area of Science:

  • Microbiology and Infectious Diseases
  • Natural Product Chemistry
  • Drug Discovery and Development

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a significant global health challenge due to widespread antibiotic resistance.
  • The urgent need for novel therapeutic agents with distinct mechanisms of action against MRSA is paramount.

Purpose of the Study:

  • To investigate the antibacterial potential of pyrimrhodomyrtone (PRM), a natural product derivative, against *Staphylococcus aureus*, including MRSA strains.
  • To elucidate the molecular mechanism underlying PRM's antibacterial activity.

Main Methods:

  • In vitro and in vivo antibacterial assays were performed to evaluate PRM's efficacy.
  • Genetic and biochemical techniques were employed to identify PRM's molecular targets and interactions.
  • Cell membrane integrity and potential depolarization were assessed.

Main Results:

  • PRM demonstrated significant antibacterial activity against *S. aureus* and MRSA isolates.
  • PRM was found to interact with and inhibit N-acetylglucosamine-6-phosphate deacetylase (NagA).
  • PRM treatment led to bacterial cell membrane depolarization and integrity disruption.

Conclusions:

  • Pyrimrhodomyrtone (PRM) is a promising natural product derivative with potent anti-MRSA activity.
  • The antibacterial action of PRM involves the inhibition of NagA and damage to the bacterial cell membrane.
  • Understanding PRM's mechanism provides a foundation for developing novel anti-MRSA therapeutics.
Keywords:
Anti-MRSA activityN-acetylglucosamine-6-phosphate deacetylaseNagAPhloroglucinol derivativePyrimirhodomyrtoneStaphylococcus aureus

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