Furoxan Nitric Oxide Donors Disperse Pseudomonas aeruginosa Biofilms, Accelerate Growth, and Repress Pyoverdine Production

Poh, WH; Barraud, N; Guglielmo, S; Lazzarato, L; Rolando, B; Fruttero, R; Rice, SA

Furoxan Nitric Oxide Donors Disperse Pseudomonas aeruginosa Biofilms, Accelerate Growth, and Repress Pyoverdine Production

Poh, WH Barraud, N Guglielmo, S Lazzarato, L Rolando, B Fruttero, R Rice, SA

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Publication Type:: Journal Article
Citation:: ACS Chemical Biology, 2017, 12 (8), pp. 2097 - 2106
Issue Date:: 2017-08-18

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Field	Value	Language
dc.contributor.author	Poh, WH	en_US
dc.contributor.author	Barraud, N	en_US
dc.contributor.author	Guglielmo, S	en_US
dc.contributor.author	Lazzarato, L	en_US
dc.contributor.author	Rolando, B	en_US
dc.contributor.author	Fruttero, R	en_US
dc.contributor.author	Rice, SA https://orcid.org/0000-0002-9486-2343	en_US
dc.date.issued	2017-08-18	en_US
dc.identifier.citation	ACS Chemical Biology, 2017, 12 (8), pp. 2097 - 2106	en_US
dc.identifier.issn	1554-8929	en_US
dc.identifier.uri	http://hdl.handle.net/10453/125658
dc.description.abstract	© 2017 American Chemical Society. The use of nitric oxide (NO) as a signal for biofilm dispersal has been shown to increase the susceptibility of many biofilms to antibiotics, promoting their eradication. The delivery of NO to biofilms can be achieved by using NO donors with different kinetics and properties of NO release that can influence their efficacy as biofilm control agents. In this study, the kinetics of three furoxan derivatives were evaluated. The effects of these NO donors, which have an advantageous pharmacological profile of slower onset with an extended duration of action, on Pseudomonas aeruginosa growth, biofilm development, and dispersal were also characterized. Compound LL4254, which showed a fast rate of NO release, induced biofilm dispersal at approximately 200 μM. While LL4212 and LL4216 have a slower rate of NO release, both compounds could induce biofilm dispersal, under the same treatment conditions, when used at higher concentrations. In addition, LL4212 and LL4216 were found to promote P. aeruginosa growth in iron-limited minimal medium, leading to a faster rate of biofilm formation and glucose utilization, and ultimately resulted in early dispersal of biofilm cells through carbon starvation. High concentrations of LL4216 also repressed production of the siderophore pyoverdine by more than 50-fold, via both NOx-dependent and NOx-independent mechanisms. The effects on growth and pyoverdine levels exerted by the furoxans appeared to be mediated by NO-independent mechanisms, suggesting functional activities of furoxans in addition to their release of NO and nitrite. Overall, this study reveals that secondary effects of furoxans are important considerations for their use as NO-releasing dispersal agents and that these compounds could be potentially redesigned as pyoverdine inhibitors.	en_US
dc.relation.ispartof	ACS Chemical Biology	en_US
dc.relation.isbasedon	10.1021/acschembio.7b00256	en_US
dc.subject.classification	Organic Chemistry	en_US
dc.subject.mesh	Biofilms	en_US
dc.subject.mesh	Pseudomonas aeruginosa	en_US
dc.subject.mesh	Sulfonamides	en_US
dc.subject.mesh	Oxadiazoles	en_US
dc.subject.mesh	Oligopeptides	en_US
dc.subject.mesh	Nitric Oxide Donors	en_US
dc.subject.mesh	Anti-Bacterial Agents	en_US
dc.subject.mesh	Biological Assay	en_US
dc.title	Furoxan Nitric Oxide Donors Disperse Pseudomonas aeruginosa Biofilms, Accelerate Growth, and Repress Pyoverdine Production	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	12	en_US
utslib.for	0303 Macromolecular and Materials Chemistry	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	03 Chemical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	closed_access
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	12	en_US

Abstract:

© 2017 American Chemical Society. The use of nitric oxide (NO) as a signal for biofilm dispersal has been shown to increase the susceptibility of many biofilms to antibiotics, promoting their eradication. The delivery of NO to biofilms can be achieved by using NO donors with different kinetics and properties of NO release that can influence their efficacy as biofilm control agents. In this study, the kinetics of three furoxan derivatives were evaluated. The effects of these NO donors, which have an advantageous pharmacological profile of slower onset with an extended duration of action, on Pseudomonas aeruginosa growth, biofilm development, and dispersal were also characterized. Compound LL4254, which showed a fast rate of NO release, induced biofilm dispersal at approximately 200 μM. While LL4212 and LL4216 have a slower rate of NO release, both compounds could induce biofilm dispersal, under the same treatment conditions, when used at higher concentrations. In addition, LL4212 and LL4216 were found to promote P. aeruginosa growth in iron-limited minimal medium, leading to a faster rate of biofilm formation and glucose utilization, and ultimately resulted in early dispersal of biofilm cells through carbon starvation. High concentrations of LL4216 also repressed production of the siderophore pyoverdine by more than 50-fold, via both NOx-dependent and NOx-independent mechanisms. The effects on growth and pyoverdine levels exerted by the furoxans appeared to be mediated by NO-independent mechanisms, suggesting functional activities of furoxans in addition to their release of NO and nitrite. Overall, this study reveals that secondary effects of furoxans are important considerations for their use as NO-releasing dispersal agents and that these compounds could be potentially redesigned as pyoverdine inhibitors.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/114726