title: Design and synthesis of fluorescent pilicides and curlicides: bioactive tools to study bacterial virulence mechanisms.
abstract: 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.
authors.affiliation: Department of Chemistry, Umeå University, 90187 Umeå, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Chorell
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: Christoffer
authors.initials: C
authors.lastname: Bengtsson
authors.forename: Sofie
authors.initials: S
authors.lastname: Edvinsson
authors.forename: Corinne K
authors.initials: CK
authors.lastname: Cusumano
authors.forename: Erik
authors.initials: E
authors.lastname: Rosenbaum
authors.forename: Lennart B Å
authors.initials: LB
authors.lastname: Johansson
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
authors.forename: Fredrik
authors.initials: F
authors.lastname: Almqvist
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D014774:Virulence
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000900:Anti-Bacterial Agents; D001896:Boron Compounds; D003374:Coumarins; D029968:Escherichia coli Proteins; D005456:Fluorescent Dyes; C030123:coumarin