Our experiments also show that exposure of bacteria to
subMIC levels of antibiotics selects de novo resistance
[50]. Importantly, the de novo mutants selected at sub-
MIC antibiotic concentration evolve resistance levels
higher than the drug concentration to which they are
exposed (Figure 2). The genetic basis for this is currently
under study but it is not uncommon and occurs with both
drugs we have so far tested (an aminoglycoside and a
fluoroquinolone).
Thus, exposure to low levels of antibiotic can enrich for
pre-existing mutants with very small fitness costs and
select de novo resistant mutants, and there is no necessary
connection between the selective antibiotic concentration
and the resistance level of the selected mutants. Because
resistant mutants selected at low levels of antibiotic must
have low fitness costs their probability of becoming fixed in
the population is accordingly relatively higher.