AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A Streptococcus

Streptococcus pyogenes (group A Streptococcus (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges fro...

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Autores principales:	Nina Tsao, Ya-Chu Chang, Sung-Yuan Hsieh, Tang-Chi Li, Ching-Chen Chiu, Hai-Han Yu, Tzu-Ching Hsu, Chih-Feng Kuo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	AR-12 group A <i>Streptococcus</i> (GAS) invasive infection synergistic effect Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/3b10fa75f6ff45cbb6cb3ce19297c43e
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spelling	oai:doaj.org-article:3b10fa75f6ff45cbb6cb3ce19297c43e2021-11-11T17:05:44ZAR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i>10.3390/ijms2221116171422-00671661-6596https://doaj.org/article/3b10fa75f6ff45cbb6cb3ce19297c43e2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11617https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067<i>Streptococcus pyogenes</i> (group A <i>Streptococcus</i> (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges from 20% to 50% in spite of antibiotics administration. AR-12, a pyrazole derivative, has been reported to inhibit the infection of viruses, intracellular bacteria, and fungi. In this report, we evaluated the bactericidal activities and mechanisms of AR-12 on GAS infection. Our in vitro results showed that AR-12 dose-dependently reduced the GAS growth, and 2.5 μg/mL of AR-12 significantly killed GAS within 2 h. AR-12 caused a remarkable reduction in nucleic acid and protein content of GAS. The expression of heat shock protein DnaK and streptococcal exotoxins was also inhibited by AR-12. Surveys of the GAS architecture by scanning electron microscopy revealed that AR-12-treated GAS displayed incomplete septa and micro-spherical structures protruding out of cell walls. Moreover, the combination of AR-12 and gentamicin had a synergistic antibacterial activity against GAS replication for both in vitro and in vivo infection. Taken together, these novel findings obtained in this study may provide a new therapeutic strategy for invasive GAS infection.Nina TsaoYa-Chu ChangSung-Yuan HsiehTang-Chi LiChing-Chen ChiuHai-Han YuTzu-Ching HsuChih-Feng KuoMDPI AGarticleAR-12group A <i>Streptococcus</i> (GAS)invasive infectionsynergistic effectBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11617, p 11617 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AR-12 group A <i>Streptococcus</i> (GAS) invasive infection synergistic effect Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	AR-12 group A <i>Streptococcus</i> (GAS) invasive infection synergistic effect Biology (General) QH301-705.5 Chemistry QD1-999 Nina Tsao Ya-Chu Chang Sung-Yuan Hsieh Tang-Chi Li Ching-Chen Chiu Hai-Han Yu Tzu-Ching Hsu Chih-Feng Kuo AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i>
description	<i>Streptococcus pyogenes</i> (group A <i>Streptococcus</i> (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges from 20% to 50% in spite of antibiotics administration. AR-12, a pyrazole derivative, has been reported to inhibit the infection of viruses, intracellular bacteria, and fungi. In this report, we evaluated the bactericidal activities and mechanisms of AR-12 on GAS infection. Our in vitro results showed that AR-12 dose-dependently reduced the GAS growth, and 2.5 μg/mL of AR-12 significantly killed GAS within 2 h. AR-12 caused a remarkable reduction in nucleic acid and protein content of GAS. The expression of heat shock protein DnaK and streptococcal exotoxins was also inhibited by AR-12. Surveys of the GAS architecture by scanning electron microscopy revealed that AR-12-treated GAS displayed incomplete septa and micro-spherical structures protruding out of cell walls. Moreover, the combination of AR-12 and gentamicin had a synergistic antibacterial activity against GAS replication for both in vitro and in vivo infection. Taken together, these novel findings obtained in this study may provide a new therapeutic strategy for invasive GAS infection.
format	article
author	Nina Tsao Ya-Chu Chang Sung-Yuan Hsieh Tang-Chi Li Ching-Chen Chiu Hai-Han Yu Tzu-Ching Hsu Chih-Feng Kuo
author_facet	Nina Tsao Ya-Chu Chang Sung-Yuan Hsieh Tang-Chi Li Ching-Chen Chiu Hai-Han Yu Tzu-Ching Hsu Chih-Feng Kuo
author_sort	Nina Tsao
title	AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i>
title_short	AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i>
title_full	AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i>
title_fullStr	AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i>
title_full_unstemmed	AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i>
title_sort	ar-12 has a bactericidal activity and a synergistic effect with gentamicin against group a <i>streptococcus</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3b10fa75f6ff45cbb6cb3ce19297c43e
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AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A <i>Streptococcus</i>

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