  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.
