دورية أكاديمية
Quinoline Compounds Targeting the
العنوان: | Quinoline Compounds Targeting the |
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المؤلفون: | Fraunfelter, Vesper M, Pugh, Bryce A, Williams, Alexander P L, Ward, Katie T, Jackson, Dietrich O, Austin, Molly, Ciprich, John F, Dippy, Lorelei, Dunford, Jason, Edwards, G Nathaniel, Glass, Evan, Handy, Kyle M, Kellogg, Casey N, Llewellyn, Kaitlyn, Nyberg, K Quinn, Shepard, Sam J, Thomas, Casey, Wolfe, Amanda L, Steed, P Ryan |
المصدر: | ACS Infect Dis ; ISSN:2373-8227 ; Volume:9 ; Issue:12 |
بيانات النشر: | American Chemical Society |
سنة النشر: | 2023 |
المجموعة: | PubMed Central (PMC) |
مصطلحات موضوعية: | ATP synthase, Pseudomonas aeruginosa, antibiotic resistance, antibiotics, bioenergetics, quinolines |
الوصف: | Pseudomonas aeruginosa (PA) is a Gram-negative, biofilm-forming bacterium and an opportunistic pathogen. The growing drug resistance of PA is a serious threat that necessitates the discovery of novel antibiotics, ideally with previously underexplored mechanisms of action. Due to their central role in cell metabolism, bacterial bioenergetic processes are of increasing interest as drug targets, especially with the success of the ATP synthase inhibitor bedaquiline to treat drug-resistant tuberculosis. Like Mycobacterium tuberculosis, PA requires F1Fo ATP synthase for growth, even under anaerobic conditions, making the PA ATP synthase an ideal drug target for the treatment of drug-resistant infection. In previous work, we conducted an initial screen for quinoline compounds that inhibit ATP synthesis activity in PA. In the present study, we report additional quinoline derivatives, including one with increased potency against PA ATP synthase in vitro and antibacterial activity against drug-resistant PA. Moreover, by expressing the PA ATP synthase in Escherichia coli, we show that mutations in the H+ binding site on the membrane-embedded rotor ring alter inhibition by the reported quinoline compounds. Identification of a potent inhibitor and its probable binding site on ATP synthase enables further development of promising quinoline derivatives into a viable treatment for drug-resistant PA infection. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
العلاقة: | https://doi.org/10.1021/acsinfecdis.3c00317Test; https://pubmed.ncbi.nlm.nih.gov/37922420Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10714390Test/ |
DOI: | 10.1021/acsinfecdis.3c00317 |
الإتاحة: | https://doi.org/10.1021/acsinfecdis.3c00317Test https://pubmed.ncbi.nlm.nih.gov/37922420Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10714390Test/ |
رقم الانضمام: | edsbas.C8C05414 |
قاعدة البيانات: | BASE |
DOI: | 10.1021/acsinfecdis.3c00317 |
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