Sprayable Biocide-Free Polyurethane Paint that Reduces Biofouling and Facilitates Removal of Pathogenic Bacteria from Surfaces.

The ability to prevent bacterial adhesion on surfaces and to facilitate the removal of bacteria once they have already contaminated or colonized a surface is important in a broad range of fundamental and applied contexts. The work reported here sought to characterize the physicochemical properties of a family of biocide-free hydrophobic polyurethane coatings containing polysiloxane segments and evaluate their ability to mitigate bacterial fouling and/or facilitate subsequent surface cleaning after exposure to pathogenic bacteria. We developed benchtop microbiological assays to characterize surface fouling and subsequent removal of bacteria after repeated (i) short-term intermittent physical contact with and (ii) longer-term continuous flow-based contact with liquid growth media containing either or , two common Gram-positive or Gram-negative bacterial pathogens, respectively.

Silyl-Lipid Functionalized -Acyl Homoserine Lactones as Modulators of Bacterial Cell-Cell Communication.

We report silyl-lipid derivatives of -acyl l-homoserine lactones (AHLs) that have nanomolar activities in LuxR-type quorum sensing receptors in Gram-negative bacterial pathogens. A collection of silyl-lipid AHLs were designed and synthesized to represent three general structural classes based on native AHL signals and synthetic LuxR-type receptor modulators. The synthetic routes feature straightforward hydrosilylation and aryl silylation reactions to access silyl-lipid groups that are not readily accessible in analogous all-carbon chemistry.

Interspecies Crosstalk via LuxI/LuxR-Type Quorum Sensing Pathways Contributes to Decreased Nematode Survival in Coinfections of and .

Quorum sensing (QS) is a prominent chemical communication mechanism used by common bacteria to regulate group behaviors at high cell density, including many processes important in pathogenesis. There is growing evidence that certain bacteria can use QS to sense not only themselves but also other species and that this crosstalk could alter collective behaviors. In the current study, we report the results of culture-based and coinfection experiments that probe interspecies interactions between the opportunistic pathogens and involving their LuxI/LuxR-type QS circuits.

Synthetic Peptides Capable of Potent Multigroup Quorum Sensing Activation and Inhibition in Both Cultures and Biofilm Communities.

The pathogen uses a chemical signaling process, i.e., quorum sensing (QS), to form robust biofilms and cause human infection.

Chemical and biomolecular insights into the agr quorum sensing system: Current progress and ongoing challenges.

is a ubiquitous bacterium that has become a major threat to human health due to its extensive toxin production and tremendous capacity for antibiotic resistance (e.g., MRSA "superbug" infections).

Abiotic Small Molecule Inhibitors and Activators of the LasR Quorum Sensing Receptor in with Potencies Comparable or Surpassing -Acyl Homoserine Lactones.

The opportunistic pathogen controls almost 10% of its genome, including myriad virulence genes, via a cell-to-cell chemical communication system called quorum sensing (QS). Small molecules that either inhibit or activate QS in represent useful research tools to study the role of this signaling pathway in infection and interrogate its viability as an antivirulence target. However, despite active research in this area over the past 20+ years, there are relatively few synthetic compounds known to strongly inhibit or activate QS in .

Regulation of an antibiotic resistance efflux pump by quorum sensing and a TetR-family repressor in .

The soil bacterium uses a single LuxI-R-type quorum-sensing system, CviI-R, to regulate genes in a cell density-dependent manner. CviI synthesizes the signal -hexanoyl-homoserine lactone (C6-HSL) and CviR is a C6-HSL-responsive cytoplasmic transcription regulator. C6-HSL-bound CviR activates dozens of genes, for example the cluster coding for an efflux pump conferring antibiotic resistance.

Genetic mapping of microbial and host traits reveals production of immunomodulatory lipids by Akkermansia muciniphila in the murine gut.

The molecular bases of how host genetic variation impacts the gut microbiome remain largely unknown. Here we used a genetically diverse mouse population and applied systems genetics strategies to identify interactions between host and microbe phenotypes including microbial functions, using faecal metagenomics, small intestinal transcripts and caecal lipids that influence microbe-host dynamics. Quantitative trait locus (QTL) mapping identified murine genomic regions associated with variations in bacterial taxa; bacterial functions including motility, sporulation and lipopolysaccharide production and levels of bacterial- and host-derived lipids.

Interactions of Bacterial Quorum Sensing Signals with Model Lipid Membranes: Influence of Membrane Composition on Membrane Remodeling.

We report the influence of membrane composition on the multiscale remodeling of multicomponent lipid bilayers initiated by contact with the amphiphilic bacterial quorum sensing signal -(3-oxo)-dodecanoyl-l-homoserine lactone (3-oxo-C12-AHL) and its anionic headgroup hydrolysis product, 3-oxo-C12-HS. We used fluorescence microscopy and quartz crystal microbalance with dissipation (QCM-D) to characterize membrane reformation that occurs when these amphiphiles are placed in contact with supported lipid bilayers (SLBs) composed of (i) 1,2-dioleoyl--glycero-3-phosphocholine (DOPC) containing varying amounts of cholesterol or (ii) mixtures of DOPC and either 1,2-dioleoyl--glycero-3-phosphoethanolamine (DOPE, a conical zwitterionic lipid) or 1,2-dioleoyl--glycero-3-phospho-l-serine (DOPS, a model anionic lipid). In general, we observe these mixed-lipid membranes to undergo remodeling events, including the formation and subsequent collapse of long tubules and the formation of hemispherical caps, upon introduction to biologically relevant concentrations of 3-oxo-C12-AHL and 3-oxo-C12-HS in ways that differ substantially from those observed in single-component DOPC membranes.

Potent pan-group quorum sensing inhibitors in revealed by N-terminal tailoring of peptidomimetics.

uses small peptides to assess its population densisty (, quorum sensing) and regulate virulence at high cell number. Here, we report the design and synthesis of peptidomimetics based on these native signals that strongly block this communication pathway in all four specificity groups of .

Small Molecules with Either Receptor-Selective or Pan-Receptor Activity in the Three LuxR-Type Receptors that Regulate Quorum Sensing in .

Quorum sensing (QS) allows bacteria to assess their local cell density using chemical signals and plays a prominent role in the ability of common pathogens to infect a host. Non-native molecules capable of attenuating bacterial QS represent useful tools to explore the role of this pathway in virulence. As individual bacterial species can have multiple QS systems and/or reside in mixed communities with other bacteria capable of QS, chemical tools that are either selective for one QS system or "pan-active" and target all QS pathways are of significant interest.

Autoinducer-fluorophore conjugates enable FRET in LuxR proteins in vitro and in cells.

Cell-to-cell signaling, or quorum sensing (QS), in many Gram-negative bacteria is governed by small molecule signals (N-acyl-L-homoserine lactones, AHLs) and their cognate receptors (LuxR-type proteins). The mechanistic underpinnings of QS in these bacteria are severely limited due to the challenges of isolating and manipulating most LuxR-type proteins. Reports of quantitative direct-binding experiments on LuxR-type proteins are scarce, and robust and generalizable methods that provide such data are largely nonexistent.

Slippery Antifouling Polymer Coatings Fabricated Entirely from Biodegradable and Biocompatible Components.

We report the design of slippery liquid-infused porous surfaces (SLIPS) fabricated from building blocks that are biodegradable, edible, or generally regarded to be biocompatible. Our approach involves infusion of lubricating oils, including food oils, into nanofiber-based mats fabricated by electrospinning or blow spinning of poly(ε-caprolactone), a hydrophobic biodegradable polymer used widely in medical implants and drug delivery devices. This approach leads to durable and biodegradable SLIPS that prevent fouling by liquids and other materials, including microbial pathogens, on objects of arbitrary shape, size, and topography.

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A synthetic peptide was found to block cell-to-cell signalling, or quorum sensing, in bacteria and be highly bioavailable in mouse tissue. The controlled release of this agent from degradable polymeric microparticles strongly inhibited skin infection in a wound model at levels that far surpassed the potency of the peptide when delivered conventionally.

Identification of small molecules that strongly inhibit bacterial quorum sensing using a high-throughput lipid vesicle lysis assay.

Strategies to both monitor and block bacterial quorum sensing (QS), and thus associated infections, are of significant interest. We developed a straightforward assay to monitor biosurfactants and lytic agents produced by bacteria under the control of QS. The method is based on the lysis of synthetic lipid vesicles containing the environmentally sensitive fluorescent dye calcein.

Slippery nanoemulsion-infused porous surfaces (SNIPS): anti-fouling coatings that can host and sustain the release of water-soluble agents.

We report the design of 'slippery' nanoemulsion-infused porous surfaces (SNIPS). These materials are strongly anti-fouling to a broad range of substances, including microorganisms. Infusion with water-in-oil nanoemulsions also endows these slippery coatings with the ability to host and control or sustain the release of water-soluble agents, including polymers, peptides, and nucleic acids, opening the door to new applications of liquid-infused materials.

Fabrication of Slippery Liquid-Infused Coatings in Flexible Narrow-Bore Tubing.

We report a layer-by-layer suction-and-flow approach that enables the fabrication of polymer-based "slippery" liquid-infused porous surfaces (SLIPS) in the confined luminal spaces of flexible, narrow-bore tubing. These SLIPS-coated tubes can prevent or strongly reduce surface fouling after prolonged contact, storage, or flow of a broad range of complex fluids and viscoelastic materials, including many that are relevant in the contexts of medical devices (e.g.

Interactions of Bacterial Quorum Sensing Signals with Model Lipid Membranes: Influence of Acyl Tail Structure on Multiscale Response.

Many common bacteria use amphiphilic -acyl-L-homoserine lactones (AHLs) as signaling molecules to coordinate group behaviors at high cell densities. Past studies demonstrate that AHLs can adsorb to and promote the remodeling of lipid membranes in ways that could underpin cell-cell or host-cell interactions. Here, we report that changes in AHL acyl tail group length and oxidation state (e.

Bacterial Quorum Sensing Signals Promote Large-Scale Remodeling of Lipid Membranes.

We report that -acyl-l-homoserine lactones (AHLs), a class of nonionic amphiphiles that common bacteria use as signals to coordinate group behaviors, can promote large-scale remodeling in model lipid membranes. Characterization of supported lipid bilayers (SLBs) of the phospholipid 1,2-dioleoyl--glycero-3-phosphocholine (DOPC) by fluorescence microscopy and quartz crystal microbalance with dissipation (QCM-D) reveals the well-studied AHL signal 3-oxo-C12-AHL and its anionic head group hydrolysis product (3-oxo-C12-HS) to promote the formation of long microtubules that can retract into hemispherical caps on the surface of the bilayer. These transformations are dynamic, reversible, and dependent upon the head group structure.

Liquid Crystal-Infused Porous Polymer Surfaces: A "Slippery" Soft Material Platform for the Naked-Eye Detection and Discrimination of Amphiphilic Species.

We report the design and characterization of liquid crystal (LC)-infused porous polymer membranes that can detect and report on the presence of natural and synthetic amphiphiles in aqueous solution. We demonstrate that thermotropic LCs can be infused into nanoporous polymer membranes to yield LC-infused surfaces that exhibit slippery behaviors in contact with a range of aqueous fluids. In contrast to conventional liquid-infused surfaces (LIS) or slippery liquid-infused porous surfaces (SLIPS) prepared using isotropic oils, aqueous solutions slide over the surfaces of these LC-infused materials at speeds that depend strongly upon the composition of the fluid, including the presence, concentration, or structure of a dissolved surfactant.