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A General Model for Toxin-Antitoxin Module Dynamics Can Explain Persister Cell Formation in E. coli

Figure 6

The antitoxin and toxin translation rates influence persister cell formation.

The parameter scans for versus in the top panels show the percentage of cells (out of 200 simulated cells) that reach a free toxin level higher than 100 during a time of 500 minutes, both for independent and interacting binding sites. The bottom panel provides a more detailed analysis of the behavior observed in the interacting binding sites model for the parameters presented in Table 1 (see also white dot in the parameter scan). The number of toxin spikes with amplitude larger than 10, detected by analyzing the time evolution of 320000 cells during a time of 500 minutes each cell are plotted. Two characteristic scaling laws are found. The first one (A) is related to regular stochastic variation, and a second one with lower probability is related to rare events where a TAT complex stays bound on the DNA for a limited time determined by the DNA binding affinity of TAT. Panel A shows an example of a typical time series of 200 minutes of regular cell dynamics. Panel B shows a similar time series containing a rare toxin spike of high amplitude, which is a potential avenue to persistence. No toxic feedback effects are included: .

doi: https://doi.org/10.1371/journal.pcbi.1003190.g006