Repositioning of a mucolytic drug to a selective antibacterial against Vibrio cholerae
| العنوان: | Repositioning of a mucolytic drug to a selective antibacterial against Vibrio cholerae |
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| المؤلفون: | In-Young Chung, You-Hee Cho, Bi-o Kim, Hyejeong Jang |
| المصدر: | Journal of Microbiology. 58:61-66 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Drug, medicine.drug_class, media_common.quotation_subject, Mutant, Antibiotics, Virulence, Biology, medicine.disease_cause, Applied Microbiology and Biotechnology, Microbiology, 03 medical and health sciences, Cholera, medicine, Vibrio cholerae, 030304 developmental biology, media_common, 0303 health sciences, 030306 microbiology, Drug Repositioning, General Medicine, Acetylcysteine, Anti-Bacterial Agents, Drug repositioning, Drug development, Antibacterial activity |
| الوصف: | Drug repositioning, the approach to explore existing drugs for use in new therapeutic indications, has emerged as an alternative drug development strategy. In this study, we found that a mucolytic drug, N-acetylcysteine (NAC) showed antibacterial activity against Vibrio cholerae. NAC can provide acid stress that selectively inhibited the growth of V. cholerae among other bacterial pathogens. To address the antibacterial mechanism of NAC against V. cholerae, six acr (acetylcys-teine-resistant) mutants were isolated from 3,118 random transposon insertion clones. The transposon insertion sites of the six mutants were mapped at the five genes. All these mutants did not display NAC resistance under acidic conditions, despite their resistance to NAC under alkaline conditions, indicating that the NAC resistance directed by the acr mutations was independent of the unusual pH-sensitivity of V. cholerae. Furthermore, all these mutants displayed attenuated virulence and reduced biofilm formation, suggesting that the acr genes are required for pathogenesis of V. cholerae. This study validates the relevance of drug repositioning for antibacterials with new modes of action and will provide an insight into a novel antibacterial therapy for V. cholerae infections to minimize side effects and resistance emergence. |
| تدمد: | 1976-3794 1225-8873 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::451568d582ba2c6a25b25092173d2abf https://doi.org/10.1007/s12275-020-9590-9 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....451568d582ba2c6a25b25092173d2abf |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 19763794 12258873 |
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