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Design and Synthesis of Fluorescent Pilicides and Curlicides: Bioactive Tools to Study Bacterial Virulence Mechanisms
Author(s) -
Chorell– Erik,
Pinkner Jerome S.,
Bengtsson Christoffer,
Edvinsson Sofie,
Cusumano Corinne K.,
Rosenbaum Erik,
Johansson Lennart B. Å.,
Hultgren Scott J.,
Almqvist Fredrik
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201103936
Subject(s) - pilus , biofilm , fluorescence , virulence , bodipy , chemistry , escherichia coli , bacteria , coumarin , biophysics , microbiology and biotechnology , combinatorial chemistry , stereochemistry , biochemistry , biology , organic chemistry , genetics , gene , physics , quantum mechanics
Pilicides and curlicides are compounds that block the formation of the virulence factors pili and curli, respectively. To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized. This was achieved by using a strategy based on structure–activity knowledge, in which key pilicide and curlicide substituents on the ring‐fused dihydrothiazolo 2‐pyridone central fragment were replaced by fluorophores. Several of the resulting fluorescent compounds had improved activities as measured in pili‐ and curli‐dependent biofilm assays. We created fluorescent pilicides and curlicides by introducing coumarin and 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐ s ‐indacene (BODIPY) fluorophores at two positions on the peptidomimetic pilicide and curlicide central fragment. Fluorescence images of the uropathogenic Escherichia coli (UPEC) strain UTI89 grown in the presence of these compounds shows that the compounds are strongly associated with the bacteria with a heterogeneous distribution.