pexiganan作用于大肠杆菌的"最低抑菌浓度"（MIC）是多少？- 警示性案例研究
What is the 'minimum inhibitory concentration' (MIC) of pexiganan acting on Escherichia coli? - A cautionary case study
摘要：
我们测量了抗菌肽pexiganan作用于大肠杆菌的最小抑菌浓度（MIC），并报告了这种测量的内在变异性。这些结果导致详细研究pexiganan对E.大肠杆菌，使用平板读数器和手动平板接种（即时间-杀灭曲线）。测量的生长曲线，连同单细胞观察和肽消耗测定，表明向该细菌的群体中添加亚MIC浓度的pexiganan杀死了一部分细胞，在该过程中降低了肽活性，同时使其余细胞不受影响。这一药效学假设表明了相当大的接种物效应，我们对此进行了量化。我们的研究结果对使用MIC作为“肽作用所需浓度的测量”表示怀疑，并显示了在人群水平上的“粗粒度”研究如何为正确规划和解释MIC测量提供重要信息。
英文摘要：
We measured the minimum inhibitory concentration (MIC) of the antimicrobial peptide pexiganan acting on Escherichia coli, and report an intrinsic variability in such measurements. These results led to a detailed study of the effect of pexiganan on the growth curve of E. coli, using a plate reader and manual plating (i.e. time-kill curves). The measured growth curves, together with single-cell observations and peptide depletion assays, suggested that addition of a sub-MIC concentration of pexiganan to a population of this bacterium killed a fraction of the cells, reducing peptide activity during the process, while leaving the remaining cells unaffected. This pharmacodynamic hypothesis suggests a considerable inoculum effect, which we quantified. Our results cast doubt on the use of the MIC as 'a measure of the concentration needed for peptide action' and show how 'coarse-grained' studies at the population level give vital information for the correct planning and interpretation of MIC measurements.
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