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Natural-Product-Derived Antimicrobial Adjuvants to Reverse Plasmid-Mediated Bacterial Resistance

Linyu Wu1, Xinyuan Zhang1, Peter Oelschlaeger2

  • 1Department of Forestry Chemical Engineering, Shaanxi Key Laboratory of Economic Plant Resources Development and Utilization, Forestry College, Northwest A&F University, Yangling, Shaanxi 712100, P. R. China.

Journal of Agricultural and Food Chemistry
|January 21, 2026
PubMed

Insights

Novel antimicrobial adjuvants can restore the effectiveness of antibiotics like β-lactams, polymyxins, and tetracyclines. This review details natural compounds that inhibit resistance mechanisms, offering hope against superbugs.

Area of Science:

  • Microbiology
  • Pharmacology
  • Biochemistry

Background:

  • Plasmid-mediated resistance mechanisms, including β-lactamases (BLs), MCRs, and TetX, significantly compromise the clinical efficacy of essential antibiotics such as β-lactams, polymyxins, and tetracyclines.
  • These resistance mechanisms pose a global threat to public health and food safety, necessitating urgent development of novel therapeutic strategies.
  • Antimicrobial adjuvants that synergize with existing antibiotics represent a promising approach to overcome acquired resistance and restore antibiotic effectiveness.

Purpose of the Study:

  • To systematically review plasmid-mediated resistance mechanisms affecting β-lactams, polymyxins, and tetracyclines.
  • To provide a comprehensive overview of natural product chemotypes that inhibit key resistance enzymes (SBLs, MBLs, MCRs, Tet(X3)/Tet(X4)) or act as antimicrobial adjuvants.
  • To establish foundational principles for developing broad-spectrum antimicrobial adjuvants against plasmid-mediated bacterial resistance.

Main Methods:

  • Systematic literature review of plasmid-mediated resistance mechanisms.
  • Identification and categorization of natural product chemotypes with inhibitory activity against specific resistance enzymes.
  • Analysis of the mechanisms of action for identified natural products as antimicrobial adjuvants.

Main Results:

  • Detailed summary of plasmid-mediated resistance mechanisms including β-lactamases (BLs), MCRs, and TetX.
  • Comprehensive catalog of natural product chemotypes capable of inhibiting SBLs, MBLs, MCRs, and Tet(X3)/Tet(X4) enzymes.
  • Elucidation of mechanisms by which natural products function as antimicrobial adjuvants, synergizing with conventional antibiotics.

Conclusions:

  • Natural products offer a viable source for developing antimicrobial adjuvants to combat plasmid-mediated resistance.
  • Targeting resistance enzymes and utilizing synergistic adjuvant effects can help reclaim the therapeutic efficacy of compromised antibiotics.
  • This review provides a framework for the rational design of novel broad-spectrum antimicrobial adjuvants to address the growing crisis of antibiotic resistance.
Keywords:
antimicrobial adjuvantsbacterial resistancenatural productsplasmid-mediated resistanceβ-lactamase inhibitors

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