Multi-drug resistance (MDR) is a severe threat to our public health and often is quoted as a slowly moving pandemic. To find a strategy for overcoming resistance, antimicrobial agents simultaneously engaging multiple targets have been highlighted. Natural AMPs evolved to eliminate a broad-spectrum of pathogens, affecting multiple targets within the invading organism. We utilized peptoid, a peptidomimetic oligomer based on N-substituted glycines, to mimic the structural and mechanistic aspects of natural AMPs. 

Activity screening of our peptoid library led to the discovery of peptoid 29, which exhibited broad-spectrum antimicrobial activity and increased selectivity. The importance of WW-motif and the balance between cationic charge and hydrophobicity was confirmed. 

This work presents the first demonstration of optical diffraction tomography (ODT) being successfully applied to monitor bacterial phenotypical changes in a real-time and label-free manner upon treatment of antimicrobial peptides (AMPs) and peptoids. Our study successfully showed that ODT could be an established imaging technique for investigating mechanisms of action of various antimicrobials.

Identification of multitarget antimicrobial mechanisms of peptoid 29 using label-free and real-time imaging with 3D optical diffraction tomography 

(All articles published in this journal are made available under the terms of the Creative Commons Attribution License (CC-BY). The CC-BY license permits use, distribution and reproduction in any medium, provided the original work is properly cited and allows the commercial use of published articles. Covers are published under the Creative Commons Attribution-Non Commercial License (CC-BY-NC). The CC-BY-NC license permits use, distribution and reproduction in any medium, for noncommercial purposes only, provided the original work is properly cited.)

Inside front cover of the article, advs. 202302483. 

(All articles published in this journal are made available under the terms of the Creative Commons Attribution License (CC-BY). The CC-BY license permits use, distribution and reproduction in any medium, provided the original work is properly cited and allows the commercial use of published articles. Covers are published under the Creative Commons Attribution-Non Commercial License (CC-BY-NC). The CC-BY-NC license permits use, distribution and reproduction in any medium, for noncommercial purposes only, provided the original work is properly cited.) 

[Reference] Minsang Kim, Yeongmi Cheon, Dongmin Shin, Jieun Choi, Josefine Eilsø Nielsen, Myeong Seon Jeong, Ho Yeon Nam, Sung-Hak Kim, Reidar Lund, Håvard Jenssen, Annelise E. Barron, Seongsoo Lee*, Jiwon Seo*, 2023, Advanced Science, 2302483. “Real-Time Monitoring of Multitarget Antimicrobial Mechanisms of Peptoids Using Label-Free Imaging with Optical Diffraction Tomography”, doi.org/10.1002/advs.202302483   

[Main Author] Minsang Kim(Gwangju Institute of Science and Technology), Yeongmi Cheon(Korea Basic Science Institute, Chungnam National University), Dongmin Shin(Gwangju Institute of Science and Technology), Seongsoo Lee*(Korea Basic Science Institute), and Jiwon Seo*(Gwangju Institute of Science and Technology)

* Contact : Professor Jiwon Seo jseo@gist.ac.kr