Key players in the genetic switch of bacteriophage TP901-1.
After infection of a sensitive host temperate phages may enter either a lytic or a lysogenic pathway leading to new phage assembly or silencing as a prophage, respectively. The decision about which pathway to enter is centered in the genetic switch of the phage. In this work, we explore the bistable genetic switch of bacteriophage TP901-1 through experiments and statistical mechanical modeling. We examine the activity of the lysogenic promoter P(R) at different concentrations of the phage repressor, CI, and compare the effect of CI on P(R) in the presence or absence of the phage-encoded MOR protein expressed from the lytic promoter P(L). We find that the presence of large amounts of MOR prevents repression of the P(R) promoter, verifying that MOR works as an antirepressor. We compare our experimental data with simulations based on previous mathematical formulations of this switch. Good agreement between data and simulations verify the model of CI repression of P(R). By including MOR in the simulations, we are able to discard a model that assumes that CI and MOR do not interact before binding together at the DNA to repress P(R). The second model of Pr repression assumes the formation of a CI:MOR complex in the cytoplasm. We suggest that a CI:MOR complex may exist in different forms that either prevent or invoke P(R) repression, introducing a new twist on mixed feedback systems.
Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Denmark.
Anne
A
Alsing
Margit
M
Pedersen
Kim
K
Sneppen
Karin
K
Hammer
D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D008242:Lysogeny / Q000235:genetics; D008957:Models, Genetic; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*; D014775:Virus Activation / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C101648:ORF1 protein, Lactococcus lactis bacteriophage TP901-1; D012097:Repressor Proteins; D014764:Viral Proteins; C076896:repressor protein C1, bacteriophage
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