title: Synthesis and activity of biomimetic biofilm disruptors.
abstract: Biofilms are often associated with human bacterial infections, and the natural tolerance of biofilms to antibiotics challenges treatment. Compounds with antibiofilm activity could become useful adjuncts to antibiotic therapy. We used norspermidine, a natural trigger for biofilm disassembly in the developmental cycle of  Bacillus subtilis , to develop guanidine and biguanide compounds with up to 20-fold increased potency in preventing biofilm formation and breaking down existing biofilms. These compounds also were active against pathogenic  Staphylococcus aureus . An integrated approach involving structure-activity relationships, protonation constants, and crystal structure data on a focused synthetic library revealed that precise spacing of positively charged groups and the total charge at physiological pH distinguish potent biofilm inhibitors.
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors: Thomas
authors: T
authors: Böttcher
authors: Ilana
authors: I
authors: Kolodkin-Gal
authors: Roberto
authors: R
authors: Kolter
authors: Richard
authors: R
authors: Losick
authors: Jon
authors: J
authors: Clardy
mesh_terms: D018441:Biofilms; D006863:Hydrogen-Ion Concentration; D018716:Molecular Mimicry; D013211:Staphylococcus aureus / Q000378:metabolism