Modeling sRNA-Regulated Plasmid Maintenance.
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 expressi...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5234814?pdf=render |
| _version_ | 1818585916056272896 |
|---|---|
| author | Chen Chris Gong Stefan Klumpp |
| author_facet | Chen Chris Gong Stefan Klumpp |
| author_sort | Chen Chris Gong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T08:44:40Z |
| format | Article |
| id | doaj.art-9c0107e423c84560b8ebb6a709eb0c01 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T08:44:40Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9c0107e423c84560b8ebb6a709eb0c012022-12-21T22:37:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01121e016970310.1371/journal.pone.0169703Modeling sRNA-Regulated Plasmid Maintenance.Chen Chris GongStefan KlumppWe 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.http://europepmc.org/articles/PMC5234814?pdf=render |
| spellingShingle | Chen Chris Gong Stefan Klumpp Modeling sRNA-Regulated Plasmid Maintenance. PLoS ONE |
| title | Modeling sRNA-Regulated Plasmid Maintenance. |
| title_full | Modeling sRNA-Regulated Plasmid Maintenance. |
| title_fullStr | Modeling sRNA-Regulated Plasmid Maintenance. |
| title_full_unstemmed | Modeling sRNA-Regulated Plasmid Maintenance. |
| title_short | Modeling sRNA-Regulated Plasmid Maintenance. |
| title_sort | modeling srna regulated plasmid maintenance |
| url | http://europepmc.org/articles/PMC5234814?pdf=render |
| work_keys_str_mv | AT chenchrisgong modelingsrnaregulatedplasmidmaintenance AT stefanklumpp modelingsrnaregulatedplasmidmaintenance |