Aggregation-Induced Emission Probe for Study of the Bactericidal Mechanism of Antimicrobial Peptides

Abstract

Multidrug resistant bacterial infection has become one of the most serious threats to human health. Antimicrobial peptides (AMPs) have been identified as potential alternatives to antibiotics owing to their excellent bactericidal activity. However, the complicated bactericidal mechanism of AMPs is still poorly understood. Fluorescence imaging has many advantages in terms of dynamic monitoring, easy operation, and high sensitivity. In this study, we developed an aggregation-induced emission (AIE)-active probe AMP-2HBT by decorating the antimicrobial peptide HHC36 (KRWWKWWRR) with an AIEgen of 2-(2-hydroxyphenyl)benzothiazole (HBT). This AIE-active probe exhibited an excellent light-up fluorescence after binding with bacteria, enabling a real-time monitoring of the binding process. Moreover, a similar time-dependent bactericidal kinetics was observed for the AIE-active probe and HHC36 peptide, which indicated that the bactericidal activity of the peptide was not compromised by decorating with the AIEgen. The bactericidal mechanism of HHC36 peptide was further investigated by super-resolution fluorescence microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM), which suggested that the probe tended to accumulate on the bacterial membrane and efficiently disrupt the membrane structure to kill both Gram-positive and -negative bacteria. This AIE-active probe thus provided a convenient tool to investigate the bactericidal mechanism of AMPs.

Biomacromolecule‐Functionalized AIEgens for Advanced Biomedical Studies

“…A) The chemical conjugate structure of the peptide KRWWKWWRR‐functionalized HBT AMP‐2HBT and its design strategy for killing the bacteria. Adapted with permission . Copyright 2018, American Chemical Society.…”

“…Adapted with permission. [73] Copyright 2018, American Chemical Society. B) The chemical conjugate structure of the peptides FFGYSAYP-DSVPMMS-and YSAYPDSVPMMS-functionalized TPE-Py (TPE-Py-FFGYSA and TPE-Py-YSA, respectively), and their bioimaging for the EphA2 cluster.…”

“…In 2018, Ren and co‐workers reported the antimicrobial peptide‐based AIEgen AMP‐2HBT for monitoring bactericidal process. It consisted of two AIEgens HBT and an antimicrobial peptide HHC36 (KRWWKWWRR) via amidation reaction ( Figure A).…”

Metabolic Syndrome, Gut Microbiome and Dietary Bioactive Peptides, an Unexplored Triad

“…AMPs are natural product of several prokaryotes and eukaryotes and so far more than 5000 such peptides are reported in the literature. 28,29,30 The most common mode of action of AMPs is dependent on their ability to interact with the negatively charged cell surface of the microbes and then insert into the hydrophobic cell membrane and disrupt it either by creating pores or making clusters. There is another class of AMPs which are absorbed (cell penetration or endocytosis) by the microbial cells and exert their activities by disrupting essential biochemical pathways.…”

Host–Guest Complexation of Amphiphilic Molecules at the Air–Water Interface Prevents Oxidation by Hydroxyl Radicals and Singlet Oxygen

“…Characterization of the oxidation products of amphiphilic monolayers at the air-water interface is another challenge, especially at the molecular level. Fluorescent methods can be used to study the overall effect of oxidation to the interfacial structures, [12] but details of the oxidation products can hardly be investigated. The detailed characterization of oxidation products is highly important to study the reaction kinetics and mechanisms.…”