Jepson, Alys; Schwarz-Linek, Jana; Ryan, Lloyd; Ryadnov, Maxim; Poon, Wilson CK. (2016). What is the ‘minimum inhibitory concentration’ (MIC) of pexiganan acting on Escherichia coli? - A cautionary case study, [dataset]. University of Edinburgh. https://doi.org/10.7488/ds/1309.
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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