Bibliographic Details
| Title: |
A cyclic adenosine monophosphate response element-binding protein inhibitor enhances the antibacterial activity of polymyxin B by inhibiting the ATP hydrolyzation activity of CrrB |
| Authors: |
Wei Huang, Jinyong Zhang, Yuzhang He, Chunxia Hu, Shumin Cheng, Huan Zeng, Manling Zheng, Huijuan Yu, Xue Liu, Quanming Zou, Ruiqin Cui |
| Source: |
Frontiers in Pharmacology, Vol 13 (2022) |
| Publisher Information: |
Frontiers Media S.A., 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
antibiotic adjuvant, Klebsiella pneumoniae, polymyxin B resistant, lipid A, lipopolysaccharide, two-component system, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
The emergence of polymyxin B (PB) resistant Gram-negative bacteria poses an important clinical and public health threat. Antibiotic adjuvants development is a complementary strategy that fills the gap in new antibiotics. Here, we described the discovery of the enhancement capacity of compound 666-15, previously identified as an inhibitor of cyclic adenosine monophosphate response element-binding protein (CREB), on the activity of PB against Klebsiella pneumoniae in vitro and in vivo. Mechanistic studies showed that this compound reduced the transcription and translation levels of genes related to lipid A modification in the presence of PB. We also identified that 666-15 reduces the ATP hydrolyzation activity of CrrB, and P151L mutation mediates the resistance of bacteria to the enhancement of 666-15. Our results demonstrated the potential of 666-15 in clinical application and support the further development of a PB synergist based on this compound. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1663-9812 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fphar.2022.949869/full; https://doaj.org/toc/1663-9812 |
| DOI: |
10.3389/fphar.2022.949869 |
| Access URL: |
https://doaj.org/article/51107a7fb5114da4835c21ab68b7d43b |
| Accession Number: |
edsdoj.51107a7fb5114da4835c21ab68b7d43b |
| Database: |
Directory of Open Access Journals |
