Repurposing azithromycin and rifampicin against Gram-negative pathogens by combination with peptide potentiators.
Acinetobacter baumannii
Anti-Bacterial Agents
/ pharmacology
Azithromycin
/ pharmacology
Cell Survival
/ drug effects
Drug Repositioning
Drug Synergism
Escherichia coli
Eukaryotic Cells
/ drug effects
Gram-Negative Bacteria
/ drug effects
Humans
Inhibitory Concentration 50
Klebsiella pneumoniae
Peptides
/ pharmacology
Rifampin
/ pharmacology
Antibiotic adjuvant
Antibiotic potentiation
Antimicrobial peptide
Combination therapy
Gram-negative bacteria
Multidrug resistance
Journal
International journal of antimicrobial agents
ISSN: 1872-7913
Titre abrégé: Int J Antimicrob Agents
Pays: Netherlands
ID NLM: 9111860
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
received:
06
06
2018
revised:
11
10
2018
accepted:
30
10
2018
pubmed:
18
11
2018
medline:
3
9
2019
entrez:
18
11
2018
Statut:
ppublish
Résumé
Gram-negative bacterial pathogens are intrinsically resistant to several antibiotics that are not able to penetrate the cell envelope barrier. The aim of this study was to identify peptides that at low concentrations induce susceptibility to these antibiotics in multidrug-resistant (MDR) Gram-negative bacterial strains of clinical relevance. Pairwise screening of 34 diverse peptides and four antibiotics (erythromycin, linezolid, rifampicin and vancomycin) with primary activity against Gram-positive bacteria identified 4 peptides that at submicromolar concentrations conferred susceptibility to rifampicin or erythromycin in Escherichia coli ATCC 25922. The identified peptides exhibited synergy with azithromycin and potentiated clindamycin in MDR E. coli ST131 and Klebsiella pneumoniae ST258. The low cytotoxicity toward eukaryotic cells (IC
Identifiants
pubmed: 30447380
pii: S0924-8579(18)30317-0
doi: 10.1016/j.ijantimicag.2018.10.025
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Peptides
0
Azithromycin
83905-01-5
Rifampin
VJT6J7R4TR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
868-872Informations de copyright
Copyright © 2018. Published by Elsevier B.V.