Structure-dependent activity of plant natural products against methicillin-resistant Staphylococcus aureus

Area of Science:

• Pharmacology
• Natural Products Chemistry
• Microbiology

Background:

• Methicillin-resistant Staphylococcus aureus (MRSA) is a critical cause of healthcare-associated infections, posing a significant threat due to evolving antibiotic resistance.
• The emergence of MRSA strains resistant to last-resort antibiotics necessitates the urgent development of novel therapeutic agents.
• Natural products represent a vital resource for discovering new drug leads and antimicrobial compounds.

Purpose of the Study:

• To review and analyze plant-derived natural products with reported anti-MRSA activity up to the end of 2022.
• To identify the most effective compounds based on inhibitory concentrations and synergistic effects with existing antibiotics.
• To explore the potential of these natural products as sources for new anti-MRSA drug development.

Main Methods:

• Comprehensive literature search for studies reporting anti-MRSA activity of plant natural products published until December 2022.
• Evaluation of reported minimum inhibitory concentrations (MICs) for identified compounds.
• Analysis of studies investigating synergistic effects between natural products and conventional antibiotics, particularly focusing on mechanisms like efflux pump inhibition.

Main Results:

• Alkaloids demonstrated additive or synergistic effects, notably by inhibiting bacterial efflux pumps.
• Phloroglucinol derivatives, including lupulone, ivesinol, rhodomyrtone, aspidinol, and hyperforin, showed significant antimicrobial activity.
• Terpenoids (e.g., parthenolide, lactopicrin, acetophenone sesquiterpenes, sphaerodiene diterpenoids), macrolides (e.g., neurymenolide A), and flavonol dicoumaroylrhamnosides also exhibited pronounced anti-MRSA effects.

Conclusions:

• Plant natural products offer a promising avenue for developing new strategies against MRSA infections.
• Specific classes like phloroglucinol derivatives and alkaloids present potent candidates for further investigation and drug development.
• Synergistic interactions and efflux pump inhibition by natural products provide valuable insights for overcoming existing antibiotic resistance mechanisms.