Microbes secrete molecules that modify their environment. Here, we demonstrate a class of synthetic disaccharide derivatives (DSDs) that mimics and dominates the activity of naturally secreted rhamnolipids by Pseudomonas aeruginosa. The DSDs exhibit the dual function of activating and inhibiting the swarming motility through a concentration-dependent activity reversal that is characteristic of signaling molecules. Whereas DSDs tethered with a saturated farnesyl group exhibit inhibition of both biofilm formation and swarming motility, with higher activities than rhamnolipids, a saturated farnesyl tethered with a sulfonate group only inhibits swarming motility but promote biofilm formation. These results identified important structural elements for controlling swarming motility, biofilm formation, and bacterial adhesion and suggest an effective chemical approach to control intertwined signaling processes that are important for biofilm formation and motilities.

We have demonstrated that specific synthetic maltose derivatives activate the swarming motility of a Pseudomonas aeruginosa nonswarming mutant (rhlA) at low concentration, but inhibit it at high concentration. Although these molecules are not microbicidal, active maltose derivatives with bulky hydrocarbon groups inhibited bacterial adhesion, and exhibited biofilm inhibition and dispersion (IC₅₀ ∼20 μM and DC₅₀ ∼30 μM, respectively). Because the swarming motility of the rhlA mutant is abolished by the lack natural rhamnolipids, the swarming activation suggests that maltose derivatives are analogues of rhamnolipids. Together, these results suggest a new approach of controlling multiple bacterial activities (bacterial adhesion, biofilm formation, and swarming motility) by a set of disaccharide-based molecules.

Ever since point groups of symmetry have been used to describe molecules after Van't Hoff and Le Bel proposed tetrahedral structures for carbon atoms in 1874, it remains difficult to design chiral molecules with polyhedral symmetry T, O, or I. Past theoretical and experimental studies have mainly accomplished molecular structures that have the conformations for satisfying the T symmetry. In this work, we present a general theoretical approach to construct rigid molecular structures that have permanently the symmetry of T, O, and I. This approach involves desymmetrizaton of the vertices or the edges of Platonic solid-shaped molecules with dissymmetric moieties. Using density functional theory (DFT) and assisted model building and energy refinement (AMBER) computational methods, the structure, the rigidity, and the symmetry of the molecule are confirmed by assessing the lowest energy conformation of the molecule, which is initially presented in a planar graph. This method successfully builds molecular structures that have the symmetry of T, O, and I. Interestingly, desymmetrization of the edges has a more stringent requirement of rigidity than desymmetrization of the vertices for affording the T, O, or I symmetry. Chirality, 2008. © 2008 Wiley-Liss, Inc.