Therapeutic Effects of Inhibitor of ompA Expression against Carbapenem-Resistant Acinetobacter baumannii Strains

The widespread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been...

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Autores principales:	Seok-Hyeon Na, Hyejin Jeon, Man-Hwan Oh, Yoo-Jeong Kim, Mingi Chu, Ill-Young Lee, Je-Chul Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Acinetobacter baumannii</i> <i>ompA</i> promoter inhibitor compound 62520 anti-virulence bacteriostatic agent Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/724d93f09e0d43f4b73a273af0c7a5a6
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spelling	oai:doaj.org-article:724d93f09e0d43f4b73a273af0c7a5a62021-11-25T17:54:51ZTherapeutic Effects of Inhibitor of <i>ompA</i> Expression against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Strains10.3390/ijms2222122571422-00671661-6596https://doaj.org/article/724d93f09e0d43f4b73a273af0c7a5a62021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12257https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The widespread of carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been previously identified as an inhibitor of the <i>ompA</i> promoter activity of <i>A. baumannii</i>, against CRAB isolates, both in vitro and in vivo. Compound 62520 was found to inhibit the <i>ompA</i> expression and biofilm formation in <i>A. baumannii</i> ATCC 17978 at sub-inhibitory concentrations in a dose-dependent manner. These inhibitory properties were also observed in clinical CRAB isolates belonging to sequence type (ST) 191. Additionally, compound 62520 exhibited a bacteriostatic activity against clinical clonal complex (CC) 208 CRAB isolates, including ST191, and ESKAPE pathogens. This bacteriostatic activity was not different between STs of CRAB isolates. Bacterial clearance was observed in mice infected with bioimaging <i>A. baumannii</i> strain 24 h after treatment with compound 62520. Compound 62520 was shown to significantly increase the survival rates of both immunocompetent and neutropenic mice infected with <i>A. baumannii</i> ATCC 17978. This compound also increased the survival rates of mice infected with clinical CRAB isolate. These results suggest that compound 62520 is a promising scaffold to develop a novel therapeutic agent against CRAB infections.Seok-Hyeon NaHyejin JeonMan-Hwan OhYoo-Jeong KimMingi ChuIll-Young LeeJe-Chul LeeMDPI AGarticle<i>Acinetobacter baumannii</i><i>ompA</i> promoter inhibitorcompound 62520anti-virulencebacteriostatic agentBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12257, p 12257 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Acinetobacter baumannii</i> <i>ompA</i> promoter inhibitor compound 62520 anti-virulence bacteriostatic agent Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	<i>Acinetobacter baumannii</i> <i>ompA</i> promoter inhibitor compound 62520 anti-virulence bacteriostatic agent Biology (General) QH301-705.5 Chemistry QD1-999 Seok-Hyeon Na Hyejin Jeon Man-Hwan Oh Yoo-Jeong Kim Mingi Chu Ill-Young Lee Je-Chul Lee Therapeutic Effects of Inhibitor of <i>ompA</i> Expression against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Strains
description	The widespread of carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been previously identified as an inhibitor of the <i>ompA</i> promoter activity of <i>A. baumannii</i>, against CRAB isolates, both in vitro and in vivo. Compound 62520 was found to inhibit the <i>ompA</i> expression and biofilm formation in <i>A. baumannii</i> ATCC 17978 at sub-inhibitory concentrations in a dose-dependent manner. These inhibitory properties were also observed in clinical CRAB isolates belonging to sequence type (ST) 191. Additionally, compound 62520 exhibited a bacteriostatic activity against clinical clonal complex (CC) 208 CRAB isolates, including ST191, and ESKAPE pathogens. This bacteriostatic activity was not different between STs of CRAB isolates. Bacterial clearance was observed in mice infected with bioimaging <i>A. baumannii</i> strain 24 h after treatment with compound 62520. Compound 62520 was shown to significantly increase the survival rates of both immunocompetent and neutropenic mice infected with <i>A. baumannii</i> ATCC 17978. This compound also increased the survival rates of mice infected with clinical CRAB isolate. These results suggest that compound 62520 is a promising scaffold to develop a novel therapeutic agent against CRAB infections.
format	article
author	Seok-Hyeon Na Hyejin Jeon Man-Hwan Oh Yoo-Jeong Kim Mingi Chu Ill-Young Lee Je-Chul Lee
author_facet	Seok-Hyeon Na Hyejin Jeon Man-Hwan Oh Yoo-Jeong Kim Mingi Chu Ill-Young Lee Je-Chul Lee
author_sort	Seok-Hyeon Na
title	Therapeutic Effects of Inhibitor of <i>ompA</i> Expression against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Strains
title_short	Therapeutic Effects of Inhibitor of <i>ompA</i> Expression against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Strains
title_full	Therapeutic Effects of Inhibitor of <i>ompA</i> Expression against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Strains
title_fullStr	Therapeutic Effects of Inhibitor of <i>ompA</i> Expression against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Strains
title_full_unstemmed	Therapeutic Effects of Inhibitor of <i>ompA</i> Expression against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Strains
title_sort	therapeutic effects of inhibitor of <i>ompa</i> expression against carbapenem-resistant <i>acinetobacter baumannii</i> strains
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/724d93f09e0d43f4b73a273af0c7a5a6
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Therapeutic Effects of Inhibitor of <i>ompA</i> Expression against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Strains

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