Efflux Attenuates the Antibacterial Activity of Q203 in Mycobacterium tuberculosis
| العنوان: | Efflux Attenuates the Antibacterial Activity of Q203 in Mycobacterium tuberculosis |
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| المؤلفون: | Jinsun Jeong, Guehye Kim, Da Eun Park, Ryangyeo Kim, Minjeong Woo, Vincent Delorme, Jichan Jang |
| المصدر: | Antimicrobial Agents and Chemotherapy. 61 |
| بيانات النشر: | American Society for Microbiology, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Tuberculosis, Pyridines, 030106 microbiology, Antitubercular Agents, Microbial Sensitivity Tests, Drug resistance, Pharmacology, Mycobacterium tuberculosis, 03 medical and health sciences, Bacterial Proteins, Piperidines, Drug tolerance, Drug Resistance, Multiple, Bacterial, Oxazines, medicine, Potency, Pharmacology (medical), biology, Chemistry, Imidazoles, medicine.disease, biology.organism_classification, 030104 developmental biology, Infectious Diseases, Verapamil, Xanthenes, Susceptibility, Efflux, Ex vivo, medicine.drug |
| الوصف: | New and improved treatments for tuberculosis (TB) are urgently needed. Recently, it has been demonstrated that verapamil, an efflux inhibitor, can reduce bacterial drug tolerance caused by efflux pump activity when administered in combination with available antituberculosis agents. The aim of this study was to evaluate the effectiveness of verapamil in combination with the antituberculosis drug candidate Q203, which has recently been developed and is currently under clinical trials as a potential antituberculosis agent. We evaluated changes in Q203 activity in the presence and absence of verapamil in vitro using the resazurin microplate assay and ex vivo using a microscopy-based phenotypic assay for the quantification of intracellular replicating mycobacteria. Verapamil increased the potency of Q203 against Mycobacterium tuberculosis both in vitro and ex vivo , indicating that efflux pumps are associated with the activity of Q203. Other efflux pump inhibitors also displayed an increase in Q203 potency, strengthening this hypothesis. Therefore, the combination of verapamil and Q203 may be a promising combinatorial strategy for anti-TB treatment to accelerate the elimination of M. tuberculosis . |
| تدمد: | 1098-6596 0066-4804 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bdc350a55dff4ea64fd453a8c648f30f https://doi.org/10.1128/aac.02637-16 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bdc350a55dff4ea64fd453a8c648f30f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10986596 00664804 |
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