Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa
Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa
OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
Soren, Odel
36eafd44-c181-43e5-a9e3-b45fee755749
Rineh, Ardeshir
9b3b5d87-023c-49a3-9290-c793e4fa07c2
Silva, Diogo G
17618973-49bf-4e82-80e1-18c8d59600dc
Cai, Yuming
ec0ec21f-cb8d-4407-aed8-01da53182083
Howlin, Robert P
f3c84990-6196-47d4-ad8a-80954ea46c7f
Allan, Raymond N.
390a7d0a-38e1-410a-8dfe-c8ef8408f5e1
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Davies, Jane C
40856a00-592a-47a1-934e-6ffa051e4435
Connett, Gary J.
55d5676c-90d8-46bf-a508-62eded276516
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Kelso, Michael J.
6afd2b75-c893-44cf-8b86-93e89e21f894
Webb, Jeremy S.
ec0a5c4e-86cc-4ae9-b390-7298f5d65f8d
1 January 2020
Soren, Odel
36eafd44-c181-43e5-a9e3-b45fee755749
Rineh, Ardeshir
9b3b5d87-023c-49a3-9290-c793e4fa07c2
Silva, Diogo G
17618973-49bf-4e82-80e1-18c8d59600dc
Cai, Yuming
ec0ec21f-cb8d-4407-aed8-01da53182083
Howlin, Robert P
f3c84990-6196-47d4-ad8a-80954ea46c7f
Allan, Raymond N.
390a7d0a-38e1-410a-8dfe-c8ef8408f5e1
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Davies, Jane C
40856a00-592a-47a1-934e-6ffa051e4435
Connett, Gary J.
55d5676c-90d8-46bf-a508-62eded276516
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Kelso, Michael J.
6afd2b75-c893-44cf-8b86-93e89e21f894
Webb, Jeremy S.
ec0a5c4e-86cc-4ae9-b390-7298f5d65f8d
Soren, Odel, Rineh, Ardeshir, Silva, Diogo G, Cai, Yuming, Howlin, Robert P, Allan, Raymond N., Feelisch, Martin, Davies, Jane C, Connett, Gary J., Faust, Saul N., Kelso, Michael J. and Webb, Jeremy S.
(2020)
Cephalosporin nitric oxide-donor prodrug DEA-C3D disperses biofilms formed by clinical cystic fibrosis isolates of Pseudomonas aeruginosa.
Journal of Antimicrobial Chemotherapy.
(doi:10.1093/jac/dkz378).
Abstract
OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
Text
dkz378
- Version of Record
More information
Accepted/In Press date: 2 August 2019
e-pub ahead of print date: 17 September 2019
Published date: 1 January 2020
Identifiers
Local EPrints ID: 436538
URI: http://eprints.soton.ac.uk/id/eprint/436538
ISSN: 0305-7453
PURE UUID: 9693cdce-d19a-4551-a3f7-71e928bcdd04
Catalogue record
Date deposited: 12 Dec 2019 17:30
Last modified: 17 Mar 2024 03:51
Export record
Altmetrics
Contributors
Author:
Odel Soren
Author:
Ardeshir Rineh
Author:
Diogo G Silva
Author:
Yuming Cai
Author:
Robert P Howlin
Author:
Raymond N. Allan
Author:
Jane C Davies
Author:
Gary J. Connett
Author:
Michael J. Kelso
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics