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Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy

Daniel Sandín1, Javier Valle2, Jordi Morata3

  • 1Systems Biology of Infection Lab, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Cerdanyola del Vallés 08193, Spain.

Pharmaceutics
|October 27, 2022
PubMed

Insights

Antimicrobial peptides (AMPs) can induce bacterial tolerance, a state that may precede resistance. This tolerance, observed in E. coli, involves morphological and physiological changes and can impact antibiotic effectiveness.

Area of Science:

  • Microbiology
  • Immunology
  • Genetics

Background:

  • Antimicrobial peptides (AMPs) are crucial components of the innate immune system.
  • AMPs, like antibiotics, can lead to bacterial resistance.
  • The potential for AMPs to induce bacterial tolerance remains unexplored.

Purpose of the Study:

  • To investigate whether AMPs can induce bacterial tolerance.
  • To characterize the effects of AMP-induced tolerance on bacterial physiology and morphology.
  • To determine if AMP tolerance influences antibiotic susceptibility.

Main Methods:

  • Treatment of *Escherichia coli* with various AMPs.
  • Morphological and physiological analysis of AMP-exposed bacteria.
  • Genomic sequencing of AMP-tolerant strains.
  • Assessment of cross-tolerance between AMPs and antibiotics.

Main Results:

  • AMP treatment induces tolerance in *E. coli*, characterized by lag phases and distinct cellular changes.
  • Tolerance varies depending on the AMP's target.
  • AMP tolerance can affect susceptibility to conventional antibiotics.
  • Genomic analysis reveals mutations in membrane composition, DNA replication, and translation in tolerant strains.

Conclusions:

  • AMPs can induce bacterial tolerance, potentially serving as a precursor to resistance.
  • AMP tolerance can lead to cross-tolerance, impacting antibiotic efficacy.
  • Monitoring AMP tolerance is critical for the therapeutic use of AMPs and understanding antibiotic resistance.
  • Mutations associated with AMP tolerance overlap with those found in antibiotic-resistant strains.
Keywords:
antimicrobial peptide LL-37antimicrobial peptidesdermaseptinpleurocidinpolymyxin Btolerance

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