Romo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis

ABSTRACT To overcome increasing bacterial resistance to conventional antibiotics, many antimicrobial peptides (AMPs) derived from host defense proteins have been developed. However, there are considerable obstacles to their application to systemic infections because of their low bioavailability. In...

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Autores principales:	Hye-Ra Lee, Deok-gyun You, Hong Kyu Kim, Jang Wook Sohn, Min Ja Kim, Jong Kuk Park, Gi Young Lee, Young Do Yoo
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	AMPR-11 antimicrobial peptide drug resistance multidrug-resistant bacteria peptide antibiotics sepsis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9c2e1890da604e4f94fcbb6937034d7e
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spelling	oai:doaj.org-article:9c2e1890da604e4f94fcbb6937034d7e2021-11-15T15:57:01ZRomo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis10.1128/mBio.03258-192150-7511https://doaj.org/article/9c2e1890da604e4f94fcbb6937034d7e2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03258-19https://doaj.org/toc/2150-7511ABSTRACT To overcome increasing bacterial resistance to conventional antibiotics, many antimicrobial peptides (AMPs) derived from host defense proteins have been developed. However, there are considerable obstacles to their application to systemic infections because of their low bioavailability. In the present study, we developed an AMP derived from Romo1 (AMPR-11) that exhibits a broad spectrum of antimicrobial activity. AMPR-11 showed remarkable efficacy against sepsis-causing bacteria, including multidrug-resistant strains, with low toxicity in a murine model of sepsis after intravenous administration. It seems that AMPR-11 disrupts bacterial membranes by interacting with cardiolipin and lipid A. From the results of this study, we suggest that AMPR-11 is a new class of agent for overcoming low efficacy in the intravenous application of AMPs and is a promising candidate to overcome multidrug resistance. IMPORTANCE Abuse of antibiotics often leads to increase of multidrug-resistant (MDR) bacteria, which threatens the life of human beings. To overcome threat of antibiotic resistance, scientists are developing a novel class of antibiotics, antimicrobial peptides, that can eradicate MDR bacteria. Unfortunately, these antibiotics have mainly been developed to cure bacterial skin infections rather than others, such as life-threatening sepsis. Major pharmaceutical companies have tried to develop antiseptic drugs; however, they have not been successful. Here, we report that AMPR-11, the antimicrobial peptide (AMP) derived from mitochondrial nonselective channel Romo1, has antimicrobial activity against Gram-positive and Gram-negative bacteria comprising many clinically isolated MDR strains. Moreover, AMPR-11 increased the survival rate in a murine model of sepsis caused by MDR bacteria. We propose that AMPR-11 could be a novel antiseptic drug candidate with a broad antimicrobial spectrum to overcome MDR bacterial infection.Hye-Ra LeeDeok-gyun YouHong Kyu KimJang Wook SohnMin Ja KimJong Kuk ParkGi Young LeeYoung Do YooAmerican Society for MicrobiologyarticleAMPR-11antimicrobial peptidedrug resistancemultidrug-resistant bacteriapeptide antibioticssepsisMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	AMPR-11 antimicrobial peptide drug resistance multidrug-resistant bacteria peptide antibiotics sepsis Microbiology QR1-502
spellingShingle	AMPR-11 antimicrobial peptide drug resistance multidrug-resistant bacteria peptide antibiotics sepsis Microbiology QR1-502 Hye-Ra Lee Deok-gyun You Hong Kyu Kim Jang Wook Sohn Min Ja Kim Jong Kuk Park Gi Young Lee Young Do Yoo Romo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis
description	ABSTRACT To overcome increasing bacterial resistance to conventional antibiotics, many antimicrobial peptides (AMPs) derived from host defense proteins have been developed. However, there are considerable obstacles to their application to systemic infections because of their low bioavailability. In the present study, we developed an AMP derived from Romo1 (AMPR-11) that exhibits a broad spectrum of antimicrobial activity. AMPR-11 showed remarkable efficacy against sepsis-causing bacteria, including multidrug-resistant strains, with low toxicity in a murine model of sepsis after intravenous administration. It seems that AMPR-11 disrupts bacterial membranes by interacting with cardiolipin and lipid A. From the results of this study, we suggest that AMPR-11 is a new class of agent for overcoming low efficacy in the intravenous application of AMPs and is a promising candidate to overcome multidrug resistance. IMPORTANCE Abuse of antibiotics often leads to increase of multidrug-resistant (MDR) bacteria, which threatens the life of human beings. To overcome threat of antibiotic resistance, scientists are developing a novel class of antibiotics, antimicrobial peptides, that can eradicate MDR bacteria. Unfortunately, these antibiotics have mainly been developed to cure bacterial skin infections rather than others, such as life-threatening sepsis. Major pharmaceutical companies have tried to develop antiseptic drugs; however, they have not been successful. Here, we report that AMPR-11, the antimicrobial peptide (AMP) derived from mitochondrial nonselective channel Romo1, has antimicrobial activity against Gram-positive and Gram-negative bacteria comprising many clinically isolated MDR strains. Moreover, AMPR-11 increased the survival rate in a murine model of sepsis caused by MDR bacteria. We propose that AMPR-11 could be a novel antiseptic drug candidate with a broad antimicrobial spectrum to overcome MDR bacterial infection.
format	article
author	Hye-Ra Lee Deok-gyun You Hong Kyu Kim Jang Wook Sohn Min Ja Kim Jong Kuk Park Gi Young Lee Young Do Yoo
author_facet	Hye-Ra Lee Deok-gyun You Hong Kyu Kim Jang Wook Sohn Min Ja Kim Jong Kuk Park Gi Young Lee Young Do Yoo
author_sort	Hye-Ra Lee
title	Romo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis
title_short	Romo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis
title_full	Romo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis
title_fullStr	Romo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis
title_full_unstemmed	Romo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis
title_sort	romo1-derived antimicrobial peptide is a new antimicrobial agent against multidrug-resistant bacteria in a murine model of sepsis
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/9c2e1890da604e4f94fcbb6937034d7e
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Romo1-Derived Antimicrobial Peptide Is a New Antimicrobial Agent against Multidrug-Resistant Bacteria in a Murine Model of Sepsis

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