Deciphering the mode of action of cell wall-inhibiting antibiotics using metabolic labeling of growing peptidoglycan in Streptococcus pyogenes
| العنوان: | Deciphering the mode of action of cell wall-inhibiting antibiotics using metabolic labeling of growing peptidoglycan in Streptococcus pyogenes |
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| المؤلفون: | Asuka Maeda, Hirokazu Arimoto, Kaori Itto, Atsushi Sugimoto |
| المصدر: | Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) Scientific Reports |
| بيانات النشر: | Nature Portfolio, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Drug, Streptococcus pyogenes, medicine.drug_class, media_common.quotation_subject, Science, Antibiotics, Peptidoglycan, Bacitracin, Biology, medicine.disease_cause, Article, Fluorescence, Microbiology, Cell wall, 03 medical and health sciences, chemistry.chemical_compound, Cell Wall, medicine, Fluorescent Dyes, media_common, Multidisciplinary, Staining and Labeling, Ramoplanin, Anti-Bacterial Agents, 030104 developmental biology, chemistry, Biochemistry, Vancomycin, Medicine, medicine.drug |
| الوصف: | Because of the scanty pipeline of antibiotics newly obtained from nature, chemical modification of established drugs is one of the major streams of current antibacterial research. Intuitive and easy-to-use assays are critical for identifying drug candidates with novel modes of action. In this study, we demonstrated that metabolic fluorescent staining of growing cell walls is a powerful tool for mode-of-action analyses of antibiotics using Streptococcus pyogenes. A set of major cell-wall-inhibiting antibiotics (bacitracin, d-cycloserine, flavomycin, oxacillin, ramoplanin, and vancomycin) was employed to validate the potential of the assay. The mechanistic differences of these antibiotics were successfully observed. For instance, d-cycloserine treatment induced fluorescently stained, excessive peripheral cell wall growth. This may indicate that the switch from the peripheral growth stage to the succeeding septal growth was disturbed by the treatment. We then applied this assay to analyze a series of vancomycin derivatives. The assay was sufficiently sensitive to detect the effects of single-site chemical modification of vancomycin on its modes of action. This metabolic fluorescent labeling method is easy to perform, especially because it does not require radiolabeled substrates. Thus, it is suitable for the preliminary evaluation of antibacterial mechanisms during antibacterial research. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::64379c907bcaf3074da5126a536cef53 https://doaj.org/article/1d871a2276204003bc1143d9c1499a58 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....64379c907bcaf3074da5126a536cef53 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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