Persistence: mechanisms for triggering and enhancing phenotypic variability

When microorganisms are exposed to lethal agents, the initial exponential decay in survival is typically followed by a slower decrease. This tailing of the survival curve is due to persister cells that have differentiated into phenotypes with reduced sensitivity to the lethal agent. We review the environmental factors that have been shown to trigger such differentiation processes, as well as the network motifs that enable the coexistence of persistent and nonpersistent cells within genetically uniform populations. Threshold amplification of noise and bi-stability from positive feedback emerge as key motifs underlying persistence.