Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Infection

Carbapenem-resistant <i>A. baumannii</i> (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effe...

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Autores principales:	Manigandan Krishnan, Joonhyeok Choi, Ahjin Jang, Young Kyung Yoon, Yangmee Kim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	antimicrobial peptide <i>A. baumannii</i> carbapenem-resistance sepsis Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/0156f4d1ee5d413193f484763957c9a9
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spelling	oai:doaj.org-article:0156f4d1ee5d413193f484763957c9a92021-11-25T17:57:27ZAntiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Infection10.3390/ijms2222125201422-00671661-6596https://doaj.org/article/0156f4d1ee5d413193f484763957c9a92021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12520https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Carbapenem-resistant <i>A. baumannii</i> (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effects. In this study, we attempted to produce safer peptide antibiotics against CRAB by reversing the parent sequence to generate R-Pro9-3 and R-Pro9-3D. Among the tested peptides, R-Pro9-3D had the most rapid and effective antibacterial activity against Gram-negative bacteria, particularly clinical CRAB isolates. Analyses of antimicrobial mechanisms based on lipopolysaccharide (LPS)-neutralization, LPS binding, and membrane depolarization, as well as SEM ultrastructural investigations, revealed that R-Pro9-3D binds strongly to LPS and impairs the membrane integrity of CRAB by effectively permeabilizing its outer membrane. R-Pro9-3D was also less cytotoxic and had better proteolytic stability than Pro9-3D and killed biofilm forming CRAB. As an LPS-neutralizing peptide, R-Pro9-3D effectively reduced LPS-induced pro-inflammatory cytokine levels in RAW 264.7 cells. The antiseptic abilities of R-Pro9-3D were also investigated using a mouse model of CRAB-induced sepsis, which revealed that R-Pro9-3D reduced multiple organ damage and attenuated systemic infection by acting as an antibacterial and immunosuppressive agent. Thus, R-Pro9-3D displays potential as a novel antiseptic peptide for treating Gram-negative CRAB infections.Manigandan KrishnanJoonhyeok ChoiAhjin JangYoung Kyung YoonYangmee KimMDPI AGarticleantimicrobial peptide<i>A. baumannii</i>carbapenem-resistancesepsisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12520, p 12520 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antimicrobial peptide <i>A. baumannii</i> carbapenem-resistance sepsis Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	antimicrobial peptide <i>A. baumannii</i> carbapenem-resistance sepsis Biology (General) QH301-705.5 Chemistry QD1-999 Manigandan Krishnan Joonhyeok Choi Ahjin Jang Young Kyung Yoon Yangmee Kim Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Infection
description	Carbapenem-resistant <i>A. baumannii</i> (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effects. In this study, we attempted to produce safer peptide antibiotics against CRAB by reversing the parent sequence to generate R-Pro9-3 and R-Pro9-3D. Among the tested peptides, R-Pro9-3D had the most rapid and effective antibacterial activity against Gram-negative bacteria, particularly clinical CRAB isolates. Analyses of antimicrobial mechanisms based on lipopolysaccharide (LPS)-neutralization, LPS binding, and membrane depolarization, as well as SEM ultrastructural investigations, revealed that R-Pro9-3D binds strongly to LPS and impairs the membrane integrity of CRAB by effectively permeabilizing its outer membrane. R-Pro9-3D was also less cytotoxic and had better proteolytic stability than Pro9-3D and killed biofilm forming CRAB. As an LPS-neutralizing peptide, R-Pro9-3D effectively reduced LPS-induced pro-inflammatory cytokine levels in RAW 264.7 cells. The antiseptic abilities of R-Pro9-3D were also investigated using a mouse model of CRAB-induced sepsis, which revealed that R-Pro9-3D reduced multiple organ damage and attenuated systemic infection by acting as an antibacterial and immunosuppressive agent. Thus, R-Pro9-3D displays potential as a novel antiseptic peptide for treating Gram-negative CRAB infections.
format	article
author	Manigandan Krishnan Joonhyeok Choi Ahjin Jang Young Kyung Yoon Yangmee Kim
author_facet	Manigandan Krishnan Joonhyeok Choi Ahjin Jang Young Kyung Yoon Yangmee Kim
author_sort	Manigandan Krishnan
title	Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Infection
title_short	Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Infection
title_full	Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Infection
title_fullStr	Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Infection
title_full_unstemmed	Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Infection
title_sort	antiseptic 9-meric peptide with potency against carbapenem-resistant <i>acinetobacter baumannii</i> infection
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0156f4d1ee5d413193f484763957c9a9
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Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Infection

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