Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa.
Adolescent
Anti-Bacterial Agents
/ pharmacology
Biofilms
/ drug effects
Cephalosporins
/ pharmacology
Cystic Fibrosis
/ microbiology
Drug Synergism
Humans
Microbial Sensitivity Tests
Middle Aged
Nitric Oxide Donors
/ pharmacology
Prodrugs
/ pharmacology
Pseudomonas Infections
/ microbiology
Pseudomonas aeruginosa
/ drug effects
Young Adult
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
01 01 2020
01 01 2020
Historique:
received:
11
04
2019
revised:
16
07
2019
accepted:
02
08
2019
pubmed:
5
11
2019
medline:
17
4
2021
entrez:
5
11
2019
Statut:
ppublish
Résumé
The cephalosporin nitric oxide (NO)-donor prodrug DEA-C3D ('DiEthylAmin-Cephalosporin-3'-Diazeniumdiolate') has been shown to initiate the dispersal of biofilms formed by the Pseudomonas aeruginosa laboratory strain PAO1. In this study, we investigated whether DEA-C3D disperses biofilms formed by clinical cystic fibrosis (CF) isolates of P. aeruginosa and its effect in combination with two antipseudomonal antibiotics, tobramycin and colistin, in vitro. β-Lactamase-triggered release of NO from DEA-C3D was confirmed using a gas-phase chemiluminescence detector. MICs for P. aeruginosa clinical isolates were determined using the broth microdilution method. A crystal violet staining technique and confocal laser scanning microscopy were used to evaluate the effects of DEA-C3D on P. aeruginosa biofilms alone and in combination with tobramycin and colistin. DEA-C3D was confirmed to selectively release NO in response to contact with bacterial β-lactamase. Despite lacking direct, cephalosporin/β-lactam-based antibacterial activity, DEA-C3D was able to disperse biofilms formed by three P. aeruginosa clinical isolates. Confocal microscopy revealed that DEA-C3D in combination with tobramycin produces similar reductions in biofilm to DEA-C3D alone, whereas the combination with colistin causes near complete eradication of P. aeruginosa biofilms in vitro. DEA-C3D is effective in dispersing biofilms formed by multiple clinical isolates of P. aeruginosa and could hold promise as a new adjunctive therapy to patients with CF.
Identifiants
pubmed: 31682251
pii: 5571146
doi: 10.1093/jac/dkz378
pmc: PMC6910178
doi:
Substances chimiques
Anti-Bacterial Agents
0
Cephalosporins
0
Nitric Oxide Donors
0
Prodrugs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
117-125Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R012415/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
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