title: Control of bacterial biofilms with marine alkaloid derivatives.
abstract: Bacterial biofilms are defined as a community of surface-attached bacteria that are protected by an extracellular matrix of biomolecules. We have recently reported the synthesis of a small molecule, denoted TAGE, based on the natural product bromoageliferin and demonstrated that TAGE has anti-biofilm activity against Pseudomonas aeruginosa. Herein we demonstrate that TAGE: (1) does not have selective toxicity against cells within the biofilm state, (2) will inhibit biofilm development under flow conditions, indicating that the CV staining protocol correlates with the ability to be active under biomimetic conditions, and (3) will disperse preformed P. aeruginosa biofilms. We also present preliminary toxicity work that indicates that TAGE is devoid of cytotoxicity in rat and mice cell lines. Advanced derivatives of TAGE have generated compounds shown to be exceedingly effective as biofilm inhibitors against the gamma-proteobacteria in this study (P. aeruginosa strains PAO1, PA14, PDO300, and Acinetobacter baumannii). TAGE derivatives also possessed anti-biofilm activity against the beta-proteobacterium Bordetella bronchiseptica (Rb50) and the Gram-positive bacterium Staphylococcus aureus;TAGE derivatives inhibited the formation of biofilms, however, some of this activity is attributed to microbicidal activity. The TAGE derivatives presented in this study, however, do not disperse pre-formed biofilms with the same efficiency as TAGE.
authors.affiliation: Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Huigens
authors.forename: Luyan
authors.initials: L
authors.lastname: Ma
authors.forename: Christopher
authors.initials: C
authors.lastname: Gambino
authors.forename: Peter D R
authors.initials: PD
authors.lastname: Moeller
authors.forename: Anne
authors.initials: A
authors.lastname: Basso
authors.forename: John
authors.initials: J
authors.lastname: Cavanagh
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wozniak
authors.forename: Christian
authors.initials: C
authors.lastname: Melander
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000215:Acylation; D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D016950:Bordetella bronchiseptica / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D007093:Imidazoles; C533873:TAGE compound