PUBLICATION
Stapling of Peptides Potentiates the Antibiotic Treatment of Acinetobacter baumannii In Vivo
- Authors
- Schouten, G.K., Paulussen, F.M., Kuipers, O.P., Bitter, W., Grossmann, T.N., van Ulsen, P.
- ID
- ZDB-PUB-220226-7
- Date
- 2022
- Source
- Antibiotics (Basel, Switzerland) 11(2): (Journal)
- Registered Authors
- Bitter, Wilbert
- Keywords
- stapled antimicrobial peptides, synergy, zebrafish larvae infection model
- MeSH Terms
- none
- PubMed
- 35203875 Full text @ Antibiotics (Basel)
Citation
Schouten, G.K., Paulussen, F.M., Kuipers, O.P., Bitter, W., Grossmann, T.N., van Ulsen, P. (2022) Stapling of Peptides Potentiates the Antibiotic Treatment of Acinetobacter baumannii In Vivo. Antibiotics (Basel, Switzerland). 11(2):.
Abstract
The rising incidence of multidrug resistance in Gram-negative bacteria underlines the urgency for novel treatment options. One promising new approach is the synergistic combination of antibiotics with antimicrobial peptides. However, the use of such peptides is not straightforward; they are often sensitive to proteolytic degradation, which greatly limits their clinical potential. One approach to increase stability is to apply a hydrocarbon staple to the antimicrobial peptide, thereby fixing them in an α-helical conformation, which renders them less exposed to proteolytic activity. In this work we applied several different hydrocarbon staples to two previously described peptides shown to act on the outer membrane, L6 and L8, and tested their activity in a zebrafish embryo infection model using a clinical isolate of Acinetobacter baumannii as a pathogen. We show that the introduction of such a hydrocarbon staple to the peptide L8 improves its in vivo potentiating activity on antibiotic treatment, without increasing its in vivo antimicrobial activity, toxicity or hemolytic activity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping