This week Dorota has been presenting a poster at the 12th International Conference on Systems Biology in Heidelberg/Mannheim.
Cooperative regulation speeds up initiation of plasmid RK2 conjugative transfer
Dorota Herman1, Christopher M Thomas2 and Dov J Stekel3
1Center for Systems Biology, School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
2School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
3Integrative Systems Biology, School of Biosciences, University of Nottingham, LE12 5RD, UK
Plasmid RK2 belongs to the group of broad host range plasmids and encodes for multi-antibiotic resistance. They can transfer themselves horizontally by conjugative transfer. A switch between expression of proteins involved either in replication or conjugation is regulated by two global regulators, KorA and KorB, which are encoded in the central control operon. This operon is autoregulated negatively and cooperatively by dimers of KorA and KorB. We seek to explore a hypothesis that could explain the evolution of cooperative autoregulation of the central control operon: a speed-up of conjugative transfer after plasmid transjection to a new host.
We have built a multi-scale model of the RK2 central control operon and its regulation of the switch between expression of proteins involved either in replication (TrfA) or conjugative transfer (Trb proteins). The model also includes plasmid replication, host cell growth and cell division. The comparison analyses were conducted between models with cooperative and non-cooperative KorA and KorB regulation of the central control operon and the switch. The analyses concerned the dynamics of protein expression of both the regulators and the conjugative transfer proteins after plasmid transjection to a new host. For the regulatory proteins KorA and KorB, the cooperative model shows a slightly faster rise time than the model without cooperativity. However, considering the time of first expression of the conjugative transfer proteins, the cooperative model is considerably faster than the model without cooperative regulation.
In conclusion, the cooperative regulation between KorA and KorB on the central control operon could have evolved as a mechanism to speed up the preparation for conjugative plasmid transfer. We also show that a small speed-up of regulatory protein expression can result in a faster speed-up of the expression of the regulated proteins.