التفاصيل البيبلوغرافية
| العنوان: |
Structure–Interaction Relationship of Polymyxins with Lung Surfactant |
| المؤلفون: |
Xukai Jiang, Nitin A. Patil, Yuwen Xu, Hasini Wickremasinghe, Qi Tony Zhou, Fanfan Zhou, Philip E. Thompson, Lushan Wang, Min Xiao, Kade D. Roberts, Tony Velkov, Jian Li |
| سنة النشر: |
2023 |
| مصطلحات موضوعية: |
Medicine, Microbiology, Pharmacology, Biotechnology, Immunology, Cancer, Infectious Diseases, molecular dynamics simulations, integrated chemical biology, global public health, generation lipopeptide antibiotics, exhibited potent activity, based permeability barrier, negative bacterial pneumonia, critical surfactant layer, lung surfactant multidrug, negative bacteria present, effectively treat gram, lung surfactant, negative bacteria, target bacteria, sequestration mechanism, resort therapy, resistant gram, rational design, pulmonary infection, novel analog, importantly pave, formidable threat |
| الوصف: |
Multidrug-resistant Gram-negative bacteria present an urgent and formidable threat to the global public health. Polymyxins have emerged as a last-resort therapy against these ‘superbugs’; however, their efficacy against pulmonary infection is poor. In this study, we integrated chemical biology and molecular dynamics simulations to examine how the alveolar lung surfactant significantly reduces polymyxin antibacterial activity. We discovered that lung surfactant is a phospholipid-based permeability barrier against polymyxins, compromising their efficacy against target bacteria. Next, we unraveled the structure–interaction relationship between polymyxins and lung surfactant, elucidating the thermodynamics that govern the penetration of polymyxins through this critical surfactant layer. Moreover, we developed a novel analog, FADDI-235, which exhibited potent activity against Gram-negative bacteria, both in the presence and absence of lung surfactant. These findings shed new light on the sequestration mechanism of lung surfactant on polymyxins and importantly pave the way for the rational design of new-generation lipopeptide antibiotics to effectively treat Gram-negative bacterial pneumonia. |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/Structure_Interaction_Relationship_of_Polymyxins_with_Lung_Surfactant/24665327 |
| DOI: |
10.1021/acs.jmedchem.3c01497.s004 |
| الاتاحة: |
https://doi.org/10.1021/acs.jmedchem.3c01497.s004
https://figshare.com/articles/dataset/Structure_Interaction_Relationship_of_Polymyxins_with_Lung_Surfactant/24665327 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.BC592A03 |
| قاعدة البيانات: |
BASE |