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Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
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Aggregation-Induced Emission Probe for Study of the Bactericidal Mechanism of Antimicrobial Peptides

Junjian Chen1,2, Meng Gao1,2, Lin Wang1,2

  • 1National Engineering Research Center for Tissue Restoration and Reconstruction , South China University of Technology , Guangzhou 510006 , China.

ACS Applied Materials & Interfaces
|March 23, 2018
PubMed

Insights

Researchers developed a novel fluorescent probe (AMP-2HBT) to visualize how antimicrobial peptides (AMPs) kill bacteria. This tool helps understand AMPs

Area of Science:

  • Biochemistry
  • Microbiology
  • Materials Science

Background:

  • Multidrug-resistant bacterial infections pose a significant global health threat.
  • Antimicrobial peptides (AMPs) show promise as antibiotic alternatives due to their potent bactericidal effects.
  • The precise mechanisms underlying AMP-induced bacterial death remain incompletely understood.

Purpose of the Study:

  • To develop a novel fluorescent probe for real-time monitoring of antimicrobial peptide (AMP) interactions with bacteria.
  • To investigate the bactericidal mechanism of the antimicrobial peptide HHC36 using the developed probe.
  • To assess if modifying AMPs with fluorescent tags affects their antimicrobial activity.

Main Methods:

  • Synthesis of an aggregation-induced emission (AIE)-active probe (AMP-2HBT) by conjugating the antimicrobial peptide HHC36 with an AIEgen (2-(2-hydroxyphenyl)benzothiazole).
  • Utilizing fluorescence imaging for real-time monitoring of probe-bacterial binding.
  • Employing super-resolution fluorescence microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) to elucidate the bactericidal mechanism.
  • Conducting time-dependent bactericidal kinetic studies.

Main Results:

  • The AIE-active probe AMP-2HBT demonstrated 'light-up' fluorescence upon binding to bacteria, enabling dynamic visualization.
  • The probe exhibited similar time-dependent bactericidal kinetics to the parent peptide HHC36, indicating preserved activity.
  • Microscopy analyses revealed probe accumulation on bacterial membranes, leading to membrane disruption and bacterial death.
  • The probe effectively killed both Gram-positive and Gram-negative bacteria.

Conclusions:

  • The developed AIE-active probe (AMP-2HBT) is a valuable tool for real-time monitoring of AMP-bacterial interactions.
  • The study provides mechanistic insights into AMP-induced bacterial membrane disruption.
  • This approach facilitates the investigation of AMP bactericidal mechanisms without compromising peptide efficacy.
Keywords:
aggregation-induced emissionantimicrobial peptidebactericidal mechanismfluorescence imagingreal-time monitoring

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