Comparison of Proteomic Responses as Global Approach to Antibiotic Mechanism of Action Elucidation.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Senges Christoph H R, Stepanek Jennifer J, Wenzel Michaela, Raatschen Nadja, Ay Ümran, Märtens Yvonne, Prochnow Pascal, Vázquez Hernández Melissa, Yayci Abdulkadir, Schubert Britta, Janzing Niklas B M, Warmuth Helen L, Kozik Martin, Bongard Jens, Alumasa John N, Albada Bauke, Penkova Maya, Lukežič Tadeja, Sorto Nohemy A, Lorenz Nicole, Miller Reece G, Zhu Bingyao, Benda Martin, Stülke Jörg, Schäkermann Sina, Leichert Lars I, Scheinpflug Kathi, Brötz-Oesterhelt Heike, Hertweck Christian, Shaw Jared T, Petković Hrvoje, Brunel Jean M, Keiler Kenneth C, Metzler-Nolte Nils, Bandow Julia E
Аннотация
New antibiotics are urgently needed to address the mounting resistance challenge. In early drug discovery, one of the bottlenecks is the elucidation of targets and mechanisms. To accelerate antibiotic research, we provide a proteomic approach for the rapid classification of compounds into those with precedented and unprecedented modes of action. We established a proteomic response library of Bacillus subtilis covering 91 antibiotics and comparator compounds, and a mathematical approach was developed to aid data analysis. Comparison of proteomic responses (CoPR) allows the rapid identification of antibiotics with dual mechanisms of action as shown for atypical tetracyclines. It also aids in generating hypotheses on mechanisms of action as presented for salvarsan (arsphenamine) and the antirheumatic agent auranofin, which is under consideration for repurposing. Proteomic profiling also provides insights into the impact of antibiotics on bacterial physiology through analysis of marker proteins indicative of the impairment of cellular processes and structures. As demonstrated for trans-translation, a promising target not yet exploited clinically, proteomic profiling supports chemical biology approaches to investigating bacterial physiology.