Daptomycin has become an important antibiotic for the treatment of serious Methicillin-Resistant Staphylococcus aureus (MRSA) infections. Unlike other approved antibiotics, its mode of action is still under active investigation, as well as the molecular basis of daptomycin resistance, which emerges in some cases during daptomycin treatment. Small nucleotide polymorphisms (SNPs) in the Multiple Peptide Resistance Factor (MprF) appear to play a major role in the resistance mechanism. Until recently, the impact of the SNPs on MprF activity has remained unclear, which is due to conflicting reports on resistance-associated phenotypes and an incomplete understanding of the mode of action of MprF. However, recent structural insights into MprF and studies with isogenic mutants have now led to a new model of MprF-mediated daptomycin resistance, which harmonizes most of the observed phenotypes and provides a basis for challenging biochemical investigations.

达托霉素已成为治疗严重耐甲氧西林金黄色葡萄球菌的重要抗生素（MRSA）感染。与其他批准的抗生素不同，它的作用方式以及达托霉素抗性的分子基础仍在积极研究中，达托霉素抗药性在某些情况下会在达托霉素治疗期间出现。多肽抗性因子（MprF）中的小核苷酸多态性（SNP）似乎在抗性机制中起主要作用。直到最近，SNPs对MprF活性的影响仍不清楚，这是由于有关耐药相关表型的报道相互矛盾以及对MprF作用方式的不完全了解。但是，对MprF的最新结构见解以及对同基因突变体的研究现在已经形成了MprF介导的达托霉素抗性的新模型，该模型可协调大多数观察到的表型，并为具有挑战性的生化研究提供了基础。