Journal of the American Chemical Society
Communication
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures, characterization data, additional
results, and complete ref 4. This material is available free of
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S
AUTHOR INFORMATION
Corresponding Author
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Figure 1. Determination of extracellular DHQ, HHQ, and PQS levels
produced by P. aeruginosa PA14 in the presence of 19 (250 μM) using
UHPLC−MS/MS. Experiments were performed twice independently.
Present Address
⊥Grunenthal Pharma GmbH, Global Drug Discovery, Ziegler-
̈
and co-workers that pqsA is the only gene within the pqsABCD
cluster that is necessary for DHQ production.15 The
physiological role of DHQ is not fully understood, but it should
be mentioned that DHQ inhibits the cell viability of mouse lung
epithelial MLE-12 cells, thereby contributing to the pathoge-
nicity of P. aeruginosa PA14.16
In P. aeruginosa it was shown that a mutant having a transposon
insertion within the pqsA gene (deficient in HHQ and PQS
production21) forms less biofilm than the wild type.22 Thus, we
tested the influence of compound 19 for its potential to interfere
with biofilm formation by P. aeruginosa PA14. Indeed, we found
that addition of 19 to a 24 h old biofilm reduced the biovolume of
the biofilm by 38% within a 24 h incubation period (Figure 2 and
Figure S2 in the SI; representative single slices of 19- and
DMSO-treated biofilms are shown in Figures S3 and S4).
str. 6, 52099 Aachen, Germany.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank Simone Amann for her help in performing the PqsD
assay, Drs. Joseph Zapp and Stefan Boettcher for NMR and MS
■
analyses, and Prof. Dr. Rolf Muller for kindly supplying
pET28a(+)/pqsD.
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dx.doi.org/10.1021/ja3072397 | J. Am. Chem. Soc. 2012, 134, 16143−16146