A molecular model for persister in E. coli.
Like many other bacteria, Escherichia coli remain as tiny viable individuals named persisters after being exposed to an antibiotic. These persisters are believed to be phenotypic heterogeneous one rather than mutants, because their progenies are as susceptible to antibiotics as their ancestors. Recently, two persister-related genes (hipB/hipA) were confirmed to belong to a toxin-antitoxin (TA) module. Their control circuit was believed to be responsible for generation of the persister subpopulation. For the well-studied TA module, we build a simple genetic regulation model to explain the phenotypic heterogeneity. We find that a sole double-negative feedback loop is not enough to explain the phenotypic heterogeneity; the cooperation mechanisms in HipB and HipA are indispensable. Moreover, our model illustrates an important persister-related experimental phenomenon: the emergence of the persister depends on the growth rate in continuous culture.
Lou
Chunbo
C
School of Physics and the Center for Theoretical Biology, Peking University, 100871 Beijing, China.
Li
Zhengyan
Z
Ouyang
Qi
Q
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000254:growth & development; D004268:DNA-Binding Proteins / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics; D005798:Genes, Bacterial; D008954:Models, Biological; D008958:Models, Molecular; D010403:Penicillin Resistance / Q000235:genetics*; D055503:Protein Multimerization
D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C070740:hipB protein, E coli; C070741:hipA protein, E coli