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In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant Acinetobacter baumannii
The increasing trend of carbapenem-resistant Acinetobacter baumannii (CRAB) worldwide has become a concern, limiting therapeutic alternatives and increasing morbidity and mortality rates. The immunomodulation agent ammonium trichloro (dioxoethylene-O,O′-) tellurate (AS101) was repurposed as an antim...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399104/ https://www.ncbi.nlm.nih.gov/pubmed/34451920 http://dx.doi.org/10.3390/ph14080823 |
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author | Yang, Tsung-Ying Tseng, Sung-Pin Dlamini, Heather Nokulunga Lu, Po-Liang Lin, Lin Wang, Liang-Chun Hung, Wei-Chun |
author_facet | Yang, Tsung-Ying Tseng, Sung-Pin Dlamini, Heather Nokulunga Lu, Po-Liang Lin, Lin Wang, Liang-Chun Hung, Wei-Chun |
author_sort | Yang, Tsung-Ying |
collection | PubMed |
description | The increasing trend of carbapenem-resistant Acinetobacter baumannii (CRAB) worldwide has become a concern, limiting therapeutic alternatives and increasing morbidity and mortality rates. The immunomodulation agent ammonium trichloro (dioxoethylene-O,O′-) tellurate (AS101) was repurposed as an antimicrobial agent against CRAB. Between 2016 and 2018, 27 CRAB clinical isolates were collected in Taiwan. The in vitro antibacterial activities of AS101 were evaluated using broth microdilution, time-kill assay, reactive oxygen species (ROS) detection and electron microscopy. In vivo effectiveness was assessed using a sepsis mouse infection model. The MIC range of AS101 for 27 CRAB isolates was from 0.5 to 32 µg/mL, which is below its 50% cytotoxicity (approximately 150 µg/mL). Bactericidal activity was confirmed using a time-kill assay. The antibacterial mechanism of AS101 was the accumulation of the ROS and the disruption of the cell membrane, which, in turn, results in cell death. The carbapenemase-producing A. baumannii mouse sepsis model showed that AS101 was a better therapeutic effect than colistin. The mice survival rate after 120 h was 33% (4/12) in the colistin-treated group and 58% (7/12) in the high-dose AS101 (3.33 mg/kg/day) group. Furthermore, high-dose AS101 significantly decreased bacterial population in the liver, kidney and spleen (all p < 0.001). These findings support the concept that AS101 is an ideal candidate for further testing in future studies. |
format | Online Article Text |
id | pubmed-8399104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83991042021-08-29 In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant Acinetobacter baumannii Yang, Tsung-Ying Tseng, Sung-Pin Dlamini, Heather Nokulunga Lu, Po-Liang Lin, Lin Wang, Liang-Chun Hung, Wei-Chun Pharmaceuticals (Basel) Article The increasing trend of carbapenem-resistant Acinetobacter baumannii (CRAB) worldwide has become a concern, limiting therapeutic alternatives and increasing morbidity and mortality rates. The immunomodulation agent ammonium trichloro (dioxoethylene-O,O′-) tellurate (AS101) was repurposed as an antimicrobial agent against CRAB. Between 2016 and 2018, 27 CRAB clinical isolates were collected in Taiwan. The in vitro antibacterial activities of AS101 were evaluated using broth microdilution, time-kill assay, reactive oxygen species (ROS) detection and electron microscopy. In vivo effectiveness was assessed using a sepsis mouse infection model. The MIC range of AS101 for 27 CRAB isolates was from 0.5 to 32 µg/mL, which is below its 50% cytotoxicity (approximately 150 µg/mL). Bactericidal activity was confirmed using a time-kill assay. The antibacterial mechanism of AS101 was the accumulation of the ROS and the disruption of the cell membrane, which, in turn, results in cell death. The carbapenemase-producing A. baumannii mouse sepsis model showed that AS101 was a better therapeutic effect than colistin. The mice survival rate after 120 h was 33% (4/12) in the colistin-treated group and 58% (7/12) in the high-dose AS101 (3.33 mg/kg/day) group. Furthermore, high-dose AS101 significantly decreased bacterial population in the liver, kidney and spleen (all p < 0.001). These findings support the concept that AS101 is an ideal candidate for further testing in future studies. MDPI 2021-08-21 /pmc/articles/PMC8399104/ /pubmed/34451920 http://dx.doi.org/10.3390/ph14080823 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yang, Tsung-Ying Tseng, Sung-Pin Dlamini, Heather Nokulunga Lu, Po-Liang Lin, Lin Wang, Liang-Chun Hung, Wei-Chun In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant Acinetobacter baumannii |
title | In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant Acinetobacter baumannii |
title_full | In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant Acinetobacter baumannii |
title_fullStr | In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant Acinetobacter baumannii |
title_full_unstemmed | In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant Acinetobacter baumannii |
title_short | In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant Acinetobacter baumannii |
title_sort | in vitro and in vivo activity of as101 against carbapenem-resistant acinetobacter baumannii |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399104/ https://www.ncbi.nlm.nih.gov/pubmed/34451920 http://dx.doi.org/10.3390/ph14080823 |
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