In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant <i>Acinetobacter baumannii</i>
The increasing trend of carbapenem-resistant <i>Acinetobacter baumannii</i> (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 rep...
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| التنسيق: | مقال |
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MDPI AG
2021-08-01
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| سلاسل: | Pharmaceuticals |
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| الوصول للمادة أونلاين: | https://www.mdpi.com/1424-8247/14/8/823 |
| _version_ | 1827684380368175104 |
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| author | Tsung-Ying Yang Sung-Pin Tseng Heather Nokulunga Dlamini Po-Liang Lu Lin Lin Liang-Chun Wang Wei-Chun Hung |
| author_facet | Tsung-Ying Yang Sung-Pin Tseng Heather Nokulunga Dlamini Po-Liang Lu Lin Lin Liang-Chun Wang Wei-Chun Hung |
| author_sort | Tsung-Ying Yang |
| collection | DOAJ |
| description | The increasing trend of carbapenem-resistant <i>Acinetobacter baumannii</i> (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 <i>A. baumannii</i> 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 <i>p</i> < 0.001). These findings support the concept that AS101 is an ideal candidate for further testing in future studies. |
| first_indexed | 2024-03-10T08:29:25Z |
| format | Article |
| id | doaj.art-9466b510dbed4c1ebc72bcf495d81390 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T08:29:25Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-9466b510dbed4c1ebc72bcf495d813902023-11-22T09:12:22ZengMDPI AGPharmaceuticals1424-82472021-08-0114882310.3390/ph14080823In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant <i>Acinetobacter baumannii</i>Tsung-Ying Yang0Sung-Pin Tseng1Heather Nokulunga Dlamini2Po-Liang Lu3Lin Lin4Liang-Chun Wang5Wei-Chun Hung6Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, TaiwanCenter for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Culinary Art, I-Shou University, Kaohsiung 84001, TaiwanDepartment of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, TaiwanDepartment of Microbiology and Immunology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanThe increasing trend of carbapenem-resistant <i>Acinetobacter baumannii</i> (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 <i>A. baumannii</i> 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 <i>p</i> < 0.001). These findings support the concept that AS101 is an ideal candidate for further testing in future studies.https://www.mdpi.com/1424-8247/14/8/823drug repurposingAS101carbapenem resistance<i>Acinetobacter baumannii</i> |
| spellingShingle | Tsung-Ying Yang Sung-Pin Tseng Heather Nokulunga Dlamini Po-Liang Lu Lin Lin Liang-Chun Wang Wei-Chun Hung In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant <i>Acinetobacter baumannii</i> Pharmaceuticals drug repurposing AS101 carbapenem resistance <i>Acinetobacter baumannii</i> |
| title | In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant <i>Acinetobacter baumannii</i> |
| title_full | In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant <i>Acinetobacter baumannii</i> |
| title_fullStr | In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant <i>Acinetobacter baumannii</i> |
| title_full_unstemmed | In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant <i>Acinetobacter baumannii</i> |
| title_short | In Vitro and In Vivo Activity of AS101 against Carbapenem-Resistant <i>Acinetobacter baumannii</i> |
| title_sort | in vitro and in vivo activity of as101 against carbapenem resistant i acinetobacter baumannii i |
| topic | drug repurposing AS101 carbapenem resistance <i>Acinetobacter baumannii</i> |
| url | https://www.mdpi.com/1424-8247/14/8/823 |
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