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Synergistic Potential of Plant Alkaloids and Intragenic Antimicrobial Peptides in Treating Multidrug-Resistant

Athamy Sarah de Paula Cruz1, Thaís Campos de Sousa1, Natália Elisabeth Kruklis1

  • 1Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasilia 71966-700, DF, Brazil.

Antibiotics (Basel, Switzerland)
|June 26, 2026
PubMed
Abstract

Insights

Combining plant alkaloids with intragenic antimicrobial peptides (IAPs) shows significant antimicrobial and anti-biofilm activity against resistant bacteria. This synergistic approach may help combat multidrug-resistant infections and extend antibiotic efficacy.

Area of Science:

  • Microbiology
  • Pharmacology
  • Biochemistry

Background:

  • Nosocomial infections caused by multidrug-resistant microorganisms are a major public health threat.
  • Antimicrobial resistance (AMR) arises from excessive antibiotic use, driving the evolution of resistant pathogens.

Purpose of the Study:

  • To evaluate the synergistic antimicrobial potential of intragenic antimicrobial peptides (IAPs) combined with plant alkaloids.
  • To assess the efficacy of these combinations against susceptible and multidrug-resistant bacterial strains, including biofilm inhibition and hemocompatibility.

Main Methods:

  • Tested molecules included berberine, tomatidine, sinomenine, and IAPs (Hs02, Gr01).
  • Minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) assays were performed against reference and clinical bacterial strains.
  • Synergistic interactions, biofilm inhibition, and hemolysis were evaluated using checkerboard assays and human red blood cells.

Main Results:

  • Alkaloid-IAP combinations reduced MICs up to 128-fold.
  • Combinations inhibited biofilm formation by 50% in *S. aureus* and *E. coli* (p < 0.05).
  • Sinomenine demonstrated previously unreported antimicrobial activity.

Conclusions:

  • Combinations of natural and synthetic bioactive molecules are promising antimicrobial candidates.
  • This strategy may help prolong the effectiveness of existing antibiotics.
  • Further research is required to evaluate safety, including cytotoxicity and in vivo effects.
Keywords:
alkaloidsantimicrobial resistancebiofilm inhibitionintragenic antimicrobial peptidessynergistic combinations

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