title: Modeling sRNA-Regulated Plasmid Maintenance.
abstract: We study a theoretical model for the toxin-antitoxin (hok/sok) mechanism for plasmid maintenance in bacteria. Toxin-antitoxin systems enforce the maintenance of a plasmid through post-segregational killing of cells that have lost the plasmid. Key to their function is the tight regulation of expression of a protein toxin by an sRNA antitoxin. Here, we focus on the nonlinear nature of the regulatory circuit dynamics of the toxin-antitoxin mechanism. The mechanism relies on a transient increase in protein concentration rather than on the steady state of the genetic circuit. Through a systematic analysis of the parameter dependence of this transient increase, we confirm some known design features of this system and identify new ones: for an efficient toxin-antitoxin mechanism, the synthesis rate of the toxin's mRNA template should be lower that of the sRNA antitoxin, the mRNA template should be more stable than the sRNA antitoxin, and the mRNA-sRNA complex should be more stable than the sRNA antitoxin. Moreover, a short half-life of the protein toxin is also beneficial to the function of the toxin-antitoxin system. In addition, we study a therapeutic scenario in which a competitor mRNA is introduced to sequester the sRNA antitoxin, causing the toxic protein to be expressed.
authors.affiliation: Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.|Institute of Physics and Astronomy, University of Potsdam, Potsdam, Germany.
authors.forename: Chen Chris
authors.identifier: http://orcid.org/0000-0002-6406-6266
authors.initials: CC
authors.lastname: Gong
authors.affiliation: Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.|Institute for Nonlinear Dynamics, Georg August University of Göttingen, Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Klumpp
mesh_terms: D000992:Antitoxins / Q000235:genetics*; D001419:Bacteria / Q000235:genetics*; D001427:Bacterial Toxins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D010957:Plasmids / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics*; D012329:RNA, Bacterial / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D016372:RNA, Antisense; D012329:RNA, Bacterial; D012333:RNA, Messenger