Ion Exchange Biomaterials to Capture Daptomycin and Prevent Resistance Evolution in Off-Target Bacterial Populations.

Daptomycin (DAP), a cyclic anionic lipopeptide antibiotic, is among the last resorts to treat multidrug-resistant Gram-positive bacterial infections, caused by vancomycin-resistant Enterococcus faecium or methicillin-resistant Staphylococcus aureus. DAP is administered intravenously, and via biliary excretion, ∼5-10% of the intravenous DAP dose arrives in the gastrointestinal (GI) tract where it drives resistance evolution in the off-target populations of E. faecium bacteria. Previously, we have shown in vivo that the oral administration of cholestyramine, an ion exchange biomaterial (IXB) sorbent, prevents DAP treatment from enriching DAP resistance in the populations of E. faecium shed from mice. Here, we investigate the biomaterial-DAP interfacial interactions to uncover the antibiotic removal mechanisms. The IXB-mediated DAP capture from aqueous media was measured in controlled pH/electrolyte solutions and in the simulated intestinal fluid (SIF) to uncover the molecular and colloidal mechanisms of DAP removal from the GI tract. Our findings show that the IXB electrostatically adsorbs the anionic antibiotic via a time-dependent diffusion-controlled process. Unsteady-state diffusion-adsorption mass balance describes the dynamics of adsorption well, and the maximum removal capacity is beyond the electric charge stoichiometric ratio because of DAP self-assembly. This study may open new opportunities for optimizing cholestyramine adjuvant therapy to prevent DAP resistance, as well as designing novel biomaterials to remove off-target antibiotics from the GI tract.

Multivariate analysis of attachment of biofouling organisms in response to material surface characteristics.

Multivariate analyses were used to investigate the influence of selected surface properties (Owens-Wendt surface energy and its dispersive and polar components, static water contact angle, conceptual sign of the surface charge, zeta potentials) on the attachment patterns of five biofouling organisms (Amphibalanus amphitrite, Amphibalanus improvisus, Bugula neritina, Ulva linza, and Navicula incerta) to better understand what surface properties drive attachment across multiple fouling organisms. A library of ten xerogel coatings and a glass standard provided a range of values for the selected surface properties to compare to biofouling attachment patterns. Results from the surface characterization and biological assays were analyzed separately and in combination using multivariate statistical methods. Principal coordinate analysis of the surface property characterization and the biological assays resulted in different groupings of the xerogel coatings. In particular, the biofouling organisms were able to distinguish four coatings that were not distinguishable by the surface properties of this study. The authors used canonical analysis of principal coordinates (CAP) to identify surface properties governing attachment across all five biofouling species. The CAP pointed to surface energy and surface charge as important drivers of patterns in biological attachment, but also suggested that differentiation of the surfaces was influenced to a comparable or greater extent by the dispersive component of surface energy.

Specific ion effects on membrane potential and the permselectivity of ion exchange membranes.

Membrane potential and permselectivity are critical parameters for a variety of electrochemically-driven separation and energy technologies. An electric potential is developed when a membrane separates electrolyte solutions of different concentrations, and a permselective membrane allows specific species to be transported while restricting the passage of other species. Ion exchange membranes are commonly used in applications that require advanced ionic electrolytes and span technologies such as alkaline batteries to ammonium bicarbonate reverse electrodialysis, but membranes are often only characterized in sodium chloride solutions. Our goal in this work was to better understand membrane behaviour in aqueous ammonium bicarbonate, which is of interest for closed-loop energy generation processes. Here we characterized the permselectivity of four commercial ion exchange membranes in aqueous solutions of sodium chloride, ammonium chloride, sodium bicarbonate, and ammonium bicarbonate. This stepwise approach, using four different ions in aqueous solution, was used to better understand how these specific ions affect ion transport in ion exchange membranes. Characterization of cation and anion exchange membrane permselectivity, using these ions, is discussed from the perspective of the difference in the physical chemistry of the hydrated ions, along with an accompanying re-derivation and examination of the basic equations that describe membrane potential. In general, permselectivity was highest in sodium chloride and lowest in ammonium bicarbonate solutions, and the nature of both the counter- and co-ions appeared to influence measured permselectivity. The counter-ion type influences the binding affinity between counter-ions and polymer fixed charge groups, and higher binding affinity between fixed charge sites and counter-ions within the membrane decreases the effective membrane charge density. As a result permselectivity decreases. The charge density and polarizability of the co-ions also appeared to influence permselectivity leading to ion-specific effects; co-ions that are charge dense and have low polarizability tended to result in high membrane permselectivity.