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Identification of Bacterial Membrane Selectivity of Romo1-Derived Antimicrobial Peptide AMPR-22 via Molecular Dynamicsopen access

Authors
Kim, HanaYoo, Young DoLee, Gi Young
Issue Date
Jul-2022
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Keywords
AMPR-22; antimicrobial peptide; molecular dynamics; extensively drug-resistant bacteria; bacterial membrane selectivity
Citation
International Journal of Molecular Sciences, v.23, no.13
Indexed
SCIE
SCOPUS
Journal Title
International Journal of Molecular Sciences
Volume
23
Number
13
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61231
DOI
10.3390/ijms23137404
ISSN
1661-6596
Abstract
The abuse or misuse of antibiotics has caused the emergence of extensively drug-resistant (XDR) bacteria, rendering most antibiotics ineffective and increasing the mortality rate of patients with bacteremia or sepsis. Antimicrobial peptides (AMPs) are proposed to overcome this problem; however, many AMPs have attenuated antimicrobial activities with hemolytic toxicity in blood. Recently, AMPR-11 and its optimized derivative, AMPR-22, were reported to be potential candidates for the treatment of sepsis with a broad spectrum of antimicrobial activity and low hemolytic toxicity. Here, we performed molecular dynamics (MD) simulations to clarify the mechanism of lower hemolytic toxicity and higher efficacy of AMPR-22 at an atomic level. We found four polar residues in AMPR-11 bound to a model mimicking the bacterial inner/outer membranes preferentially over eukaryotic plasma membrane. AMPR-22 whose polar residues were replaced by lysine showed a 2-fold enhanced binding affinity to the bacterial membrane by interacting with bacterial specific lipids (lipid A or cardiolipin) via hydrogen bonds. The MD simulations were confirmed experimentally in models that partially mimic bacteremia conditions in vitro and ex vivo. The present study demonstrates why AMPR-22 showed low hemolytic toxicity and this approach using an MD simulation would be helpful in the development of AMPs.
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