FIGURE 2.

Schematic representation of persister cell formation in Caulobacter crescentus. It has been proposed that antibiotic persistence in C. crescentus is promoted by HipA1 and HipA2 toxins, which are serine/threonine kinases that phosphorylate the aminoacyl‐tRNA synthetases GltX and TrpS, preventing synthesis of charged tRNAs (Huang et al., 2020). Phosphorylation of GltX/TrpS leads to translation arrest and activation of the amino acid starvation‐signaling pathway (SpoT). Activation of SpoT is also stochastically triggered by carbon or nitrogen starvation (indicated by the dashed arrow). Elevated levels of (p)ppGpp, a stringent response alarmone, contribute to translational arrest. Activation of SpoT and further transcriptional changes in the isogenic population of C. crescentus allow most cells to adapt to the starvation conditions, whereas only a fraction of the population becomes dormant (phenotypic heterogeneity). Dormant cells (blue cells) are not metabolically active and can survive high doses of antibiotics. The persister state is reversible; therefore, when the optimal conditions arrive, dormant cells can repopulate the environment (orange cells). The gradient red‐colored bar indicates starvation stress