Peptidomimetic antibiotics disrupt the lipopolysaccharide transport bridge of drug-resistant Enterobacteriaceae.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
24 05 2023
24 05 2023
Historique:
medline:
26
5
2023
pubmed:
24
5
2023
entrez:
24
5
2023
Statut:
ppublish
Résumé
The rise of antimicrobial resistance poses a substantial threat to our health system, and, hence, development of drugs against novel targets is urgently needed. The natural peptide thanatin kills Gram-negative bacteria by targeting proteins of the lipopolysaccharide transport (Lpt) machinery. Using the thanatin scaffold together with phenotypic medicinal chemistry, structural data, and a target-focused approach, we developed antimicrobial peptides with drug-like properties. They exhibit potent activity against Enterobacteriaceae both in vitro and in vivo while eliciting low frequencies of resistance. We show that the peptides bind LptA of both wild-type and thanatin-resistant
Identifiants
pubmed: 37224246
doi: 10.1126/sciadv.adg3683
pmc: PMC10208570
doi:
Substances chimiques
Lipopolysaccharides
0
Peptidomimetics
0
Anti-Bacterial Agents
0
LptA protein, E coli
0
Carrier Proteins
0
Escherichia coli Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadg3683Références
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