Daptomycin is a lipopeptide antibiotic that is important in the treatment of infections with Gram-positive bacteria. In the presence of calcium, daptomycin binds to phosphatidylglycerol in the bacterial cytoplasmic membrane and then forms oligomers that mediate its bactericidal effect. The structure of these bactericidal oligomers has not been elucidated. We here explore the feasibility of structural studies on the oligomer by solution-state NMR. To this end, we use nanodiscs that contain DMPC and DMPG, stabilized with a styrene-maleic acid copolymer that has been modified to minimize calcium chelation. We show that these nanodiscs bind daptomycin and induce the formation of stable oligomers under physiologically relevant conditions. The findings suggest that this membrane model is suitable for structural and functional characterization of oligomeric daptomycin, and possibly of other calcium-dependent lipopeptide antibiotics. We show that these nanodiscs bind daptomycin and induce the formation of stable oligomers, under conditions that are suitable for biomolecular NMR. The findings suggest that this membrane model is suitable for structural elucidation of oligomeric daptomycin, and possibly of other calcium-dependent lipopeptide antibiotics.

达托霉素是脂肽抗生素，在治疗革兰氏阳性细菌感染中很重要。在钙的存在下，达托霉素与细菌细胞质膜中的磷脂酰甘油结合，然后形成介导其杀菌作用的寡聚物。这些细菌低聚物的结构尚未阐明。我们在这里探索通过溶液态NMR对低聚物进行结构研究的可行性。为此，我们使用包含DMPC和DMPG的纳米光盘，并用经过改性的苯乙烯-马来酸共聚物进行稳定化处理，以最大程度地减少钙螯合。我们表明这些纳米光盘结合达托霉素，并在生理上相关的条件下诱导稳定的寡聚物的形成。这些发现表明该膜模型适合寡聚达托霉素以及可能的其他钙依赖性脂肽抗生素的结构和功能表征。我们表明这些纳米光盘结合达托霉素，并在适合生物分子NMR的条件下诱导形成稳定的低聚物。研究结果表明，这种膜模型适用于寡聚达托霉素以及可能的其他钙依赖性脂肽抗生素的结构解析。