التفاصيل البيبلوغرافية
| العنوان: |
Evaluation of the Organotellurium Compound AS101 for Treating Colistin- and Carbapenem-Resistant Klebsiella pneumoniae |
| المؤلفون: |
Tsung-Ying Yang, Hao-Yun Kao, Po-Liang Lu, Pei-Yu Chen, Shu-Chi Wang, Liang-Chun Wang, Ya-Ju Hsieh, Sung-Pin Tseng |
| المصدر: |
Pharmaceuticals; Volume 14; Issue 8; Pages: 795 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2021 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
carbapenem resistance, colistin resistance, Klebsiella pneumoniae, sepsis mouse model, AS101, drug repurposing |
| الوصف: |
Colistin- and carbapenem-resistant Enterobacteriaceae cases are increasing at alarming rates worldwide. Drug repurposing is receiving greater attention as an alternative approach in light of economic and technical barriers in antibiotics research. The immunomodulation agent ammonium trichloro(dioxoethylene-O,O’-)tellurate (AS101) was repurposed as an antimicrobial agent against colistin- and carbapenem-resistant Klebsiella pneumoniae (CRKP). 134 CRKP isolates were collected between 2012 and 2015 in Taiwan. The in vitro antibacterial activities of AS101 was observed through broth microdilution, time-kill assay, and electron microscopy. Pharmaceutical manipulation and RNA microarray were applied to investigate these antimicrobial mechanisms. Caenorhabditis elegans, a nematode animal model, and the Institute for Cancer Research (ICR) mouse model was employed for the evaluation of in vivo efficacy. The in vitro antibacterial results were found for AS101 against colistin- and CRKP isolates, with minimum inhibitory concentration (MIC) values ranging from <0.5 to 32 μg/mL. ROS-mediated antibacterial activity eliminated 99.9% of bacteria within 2–4 h. AS101 also extended the median survival time in a C. elegans animal model infected with a colistin-resistant CRKP isolate and rescued lethally infected animals in a separate mouse model of mono-bacterial sepsis by eliminating bacterial organ loads. These findings support the use of AS101 as an antimicrobial agent for addressing the colistin and carbapenem resistance crisis. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
https://dx.doi.org/10.3390/ph14080795 |
| DOI: |
10.3390/ph14080795 |
| الاتاحة: |
https://doi.org/10.3390/ph14080795 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.A2820DCD |
| قاعدة البيانات: |
BASE |