한빛사논문
Minsang Kim 1, Yeongmi Cheon 2,3,4, Dongmin Shin 1, Jieun Choi 1, Josefine Eilsø Nielsen 5,6, Myeong Seon Jeong 7, Ho Yeon Nam 1, Sung-Hak Kim 3, Reidar Lund 8, Håvard Jenssen 5, Annelise E Barron 6, Seongsoo Lee 2,9, Jiwon Seo 1
1Department of Chemistry, Gwangju Institute of Science and Technology (GIST), 123, Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Republic of Korea.
2Gwangju Center, Korea Basic Science Institute (KBSI), 49, Dosicheomdansaneop-ro, Nam-gu, Gwangju, 61751, Republic of Korea.
3Laboratory of Molecular Biochemistry, Chonnam National University, 77, Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea.
4Department of Microbiology and Molecular Biology, Chungnam National University, 99, Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.
5Department of Science and Environment, Roskilde University, Universitetsvej 1, Roskilde, 4000, Denmark.
6Department of Bioengineering, Schools of Medicine and Engineering, Stanford University, 443 Via Ortega, Stanford, California, 94305, United States.
7Chuncheon Center, Korea Basic Science Institute (KBSI), 1, Kangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, Republic of Korea.
8Department of Chemistry, University of Oslo, Problemveien 7, Oslo, 0315, Norway.
9Department of Systems Biotechnology, Chung-Ang University, Anseong-si, Gyeonggi-do, 17546, Republic of Korea.
CORRESPONDING AUTHOR : Seongsoo Lee, Jiwon Seo
Abstract
Antimicrobial peptides (AMPs) are promising therapeutics in the fight against multidrug-resistant bacteria. As a mimic of AMPs, peptoids with N-substituted glycine backbone have been utilized for antimicrobials with resistance against proteolytic degradation. Antimicrobial peptoids are known to kill bacteria by membrane disruption; however, the nonspecific aggregation of intracellular contents is also suggested as an important bactericidal mechanism. Here,structure-activity relationship (SAR) of a library of indole side chain-containing peptoids resulting in peptoid 29 as a hit compound is investigated. Then, quantitative morphological analyses of live bacteria treated with AMPs and peptoid 29 in a label-free manner using optical diffraction tomography (ODT) are performed. It is unambiguously demonstrated that both membrane disruption and intracellular biomass flocculation are primary mechanisms of bacterial killing by monitoring real-time morphological changes of bacteria. These multitarget mechanisms and rapid action can be a merit for the discovery of a resistance-breaking novel antibiotic drug.
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