Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells.
Authors
Morkunas, B
Gal, B
Galloway, Warren
Hodgkinson, James
Ibbeson, BM
Tan, YS
Publication Date
2016-07-11Journal Title
Beilstein Journal of Organic Chemistry
ISSN
1860-5397
Publisher
Beilstein-Institut
Volume
12
Pages
1428-1433
Language
English
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Morkunas, B., Gal, B., Galloway, W., Hodgkinson, J., Ibbeson, B., Tan, Y., Welch, M., & et al. (2016). Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells.. Beilstein Journal of Organic Chemistry, 12 1428-1433. https://doi.org/10.3762/bjoc.12.137
Abstract
Pyocyanin is a small molecule produced by Pseudomonas aeruginosa that plays a crucial role in the pathogenesis of infections by this notorious opportunistic pathogen. The inhibition of pyocyanin production has been identified as an attractive antivirulence strategy for the treatment of P. aeruginosa infections. Herein, we report the discovery of an inhibitor of pyocyanin production in cultures of wild-type P. aeruginosa which is based around a 4-alkylquinolin-2(1H)-one scaffold. To the best of our knowledge, this is the first reported example of pyocyanin inhibition by a compound based around this molecular framework. The compound may therefore be representative of a new structural sub-class of pyocyanin inhibitors, which could potentially be exploited in in a therapeutic context for the development of critically needed new antipseudomonal agents. In this context, the use of wild-type cells in this study is notable, since the data obtained are of direct relevance to native situations. The compound could also be of value in better elucidating the role of pyocyanin in P. aeruginosa infections. Evidence suggests that the active compound reduces the level of pyocyanin production by inhibiting the cell-cell signalling mechanism known as quorum sensing. This could have interesting implications; quorum sensing regulates a range of additional elements associated with the pathogenicity of P. aeruginosa and there is a wide range of other potential applications where the inhibition of quorum sensing is desirable.
Keywords
Pseudomonas aeruginosa, antibacterial, antivirulence, pyocyanin, quorum sensing
Sponsorship
The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no [279337/DOS]. In addition, the group research was supported by grants from the Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Medical Research Council and Welcome Trust. Y.S.T. was supported by an A*STAR Graduate Scholarship.
Funder references
European Commission (626191)
EPSRC (EP/K039520/1)
European Research Council (279337)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.3762/bjoc.12.137
This record's URL: https://www.repository.cam.ac.uk/handle/1810/260732
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International