Quantifying Stress-induced Mutagenesis

Exposure to low concentrations of antimicrobials selects for resistance mutations and can induce phenotypic stress responses in microbes. Some of these responses increase the mutation rate, called stress-induced mutagenesis (SIM). But because stress responses additionally influence the whole population dynamics it is unclear whether SIM actually results in more or fewer resistant mutants. Moreover, SIM affects mutation rate estimates via fluctuation assays (a standard lab approach for measuring microbial mutation rates) because underlying modelling assumptions are not met. We describe an appropriate model of a microbial population which is exposed to stress and expresses a stress response and propose a new method for inferring the mutation rate in this case. Using the bacterial SOS response as an example we demonstrate that our derived mutant count distribution fits simulated data. In contrast, current methods are able to estimate the mean mutation rate in the population but not distinct mutation rates of subpopulations with low/high stress response levels.