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A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant Bacteria

Authors
You, Deok-GyunLee, Hye-RaKim, Hong-KyuLee, Gi-YoungYoo, Young-Do
Issue Date
Aug-2021
Publisher
MDPI
Keywords
AMPR-11; Romo1; peptide antibiotics; drug resistance; multidrug-resistant bacteria; sepsis
Citation
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.22, no.15
Indexed
SCIE
SCOPUS
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume
22
Number
15
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/137067
DOI
10.3390/ijms22158243
ISSN
1661-6596
1422-0067
Abstract
The emergence of multidrug-resistant (MDR) bacteria through the abuse and long-term use of antibiotics is a serious health problem worldwide. Therefore, novel antimicrobial agents that can cure an infection from MDR bacteria, especially gram-negative bacteria, are urgently needed. Antimicrobial peptides, part of the innate immunity system, have been studied to find bactericidal agents potent against MDR bacteria. However, they have many problems, such as restrained systemic activity and cytotoxicity. In a previous study, we suggested that the K58-R78 domain of Romo1, a mitochondrial protein encoded by the nucleus, was a promising treatment candidate for sepsis caused by MDR bacteria. Here, we performed sequence optimization to enhance the antimicrobial activity of this peptide and named it as AMPR-22 (antimicrobial peptide derived from Romo1). It showed broad-spectrum antimicrobial activity against 17 sepsis-causing bacteria, including MDR strains, by inducing membrane permeabilization. Moreover, treatment with AMPR-22 enabled a remarkable survival rate in mice injected with MDR bacteria in a murine model of sepsis. Based on these results, we suggest that AMPR-22 could be prescribed as a first-line therapy (prior to bacterial identification) for patients diagnosed with sepsis.
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