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

Abstract

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.

Mussel-Inspired Nanocellulose Coating for Selective Neodymium Recovery

“…(i) A possible coordination between Nd 3+ and COO – groups results in the strong binding of Nd 3+ to MINC-treated SG, partially remaining unaffected by pH. (ii) According to Le Chatelier’s principle, ,, the equilibrium reactions (rxn.) regulating the adsorption process are…”

Modeling separation of lanthanides via heterogeneous ligand binding

“…Separating the chemically similar Ln 3+ from each other is a technologically relevant and chemically challenging problem. [3][4][5][6][7] Much experimental 3,[5][6][7][8][9][10][11][12][13] and theoretical work [14][15][16][17][18][19][20][21] has focused on this separation issue using organic ligands, sometimes in organic solvents. In this work, we investigate the use of simple ligands dissolved in water, or tethered to silica and metal-organic framework interior surfaces in aqueous media, to illustrate fundamental principles that lead to differential Ln 3+ binding free energies relevant to separation.…”