Imperial College London
Alternate

ProfessorJaneDavies

Faculty of Medicine, National Heart & Lung Institute

Professor of Paediatric Respirology & Experimental Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7973j.c.davies

 
 
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Assistant

 

Mrs Gina Rivellini +44 (0)20 7594 7986

 
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Location

 

G44Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Soren:2020:jac/dkz378,
author = {Soren, O and Rineh, A and Silva, DG and Cai, Y and Howlin, RP and Allan, RN and Feelisch, M and Davies, JC and Connett, GJ and Faust, SN and Kelso, MJ and Webb, JS},
doi = {jac/dkz378},
journal = {Journal of Antimicrobial Chemotherapy},
pages = {117--125},
title = {Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa},
url = {http://dx.doi.org/10.1093/jac/dkz378},
volume = {75},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - ObjectivesThe 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.Methodsβ-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.ResultsDEA-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.ConclusionsDEA-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.
AU  - Soren,O
AU  - Rineh,A
AU  - Silva,DG
AU  - Cai,Y
AU  - Howlin,RP
AU  - Allan,RN
AU  - Feelisch,M
AU  - Davies,JC
AU  - Connett,GJ
AU  - Faust,SN
AU  - Kelso,MJ
AU  - Webb,JS
DO  - jac/dkz378
EP  - 125
PY  - 2020///
SN  - 0305-7453
SP  - 117
TI  - Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa
T2  - Journal of Antimicrobial Chemotherapy
UR  - http://dx.doi.org/10.1093/jac/dkz378
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000522635100016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://academic.oup.com/jac/article/75/1/117/5571146
UR  - http://hdl.handle.net/10044/1/82746
VL  - 75
ER  -
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