Back to Search
Start Over
Proline Hinged Amphipathic α-Helical Peptide Sensitizes Gram-Negative Bacteria to Various Gram-Positive Antibiotics.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2020 Dec 10; Vol. 63 (23), pp. 14937-14950. Date of Electronic Publication: 2020 Nov 18. - Publication Year :
- 2020
-
Abstract
- Gram-negative bacteria are becoming resistant to almost all currently available antibiotics. Systemically designed antimicrobial peptides (AMPs) are attractive agents to enhance the activities of antibiotics. We constructed a small Pro-scanning library using amphipathic model peptides. Measurements of minimum inhibitory concentration (MIC) against Escherichia coli and hemolytic activities showed that one of the Pro-hinged peptides, KL-L9P, displays the highest specificity toward E. coli . Moreover, KL-L9P sensitizes E. coli to be responsive to most antibiotics that are not active against Gram-negative bacteria. The results of biochemical experiments show that KL-L9P promotes the rearrangement of the bacterial membrane that enables hydrophobic antibiotics to permeate. Finally, the results of animal tests demonstrate that KL-L9P strongly sensitizes Gram-negative bacteria to linezolid (Lzd), rifampicin (Rif), or clarithromycin (Clr). Thus, KL-L9P operates as a sensitizer to extend the antibacterial activity of most antibiotics to Gram-negative bacteria.
- Subjects :
- Animals
Anti-Bacterial Agents chemistry
Antimicrobial Cationic Peptides chemistry
Antimicrobial Cationic Peptides metabolism
Cell Membrane drug effects
Clarithromycin pharmacology
Female
Hemolysis drug effects
Humans
Hydrophobic and Hydrophilic Interactions
Linezolid pharmacology
Lipid A metabolism
Membrane Fluidity drug effects
Mice, Inbred ICR
Microbial Sensitivity Tests
Proline chemistry
Protein Binding
Protein Conformation, alpha-Helical
Rifampin pharmacology
Anti-Bacterial Agents pharmacology
Antimicrobial Cationic Peptides pharmacology
Escherichia coli drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 63
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33205989
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.0c01506