Modeling of the genetic switch of bacteriophage TP901-1: A heteromer of CI and MOR ensures robust bistability

TL;DR

This paper models the genetic switch of bacteriophage TP901-1, showing that a heteromer of CI and MOR proteins in the cytoplasm ensures robust bistability, differing from the lambda phage mechanism.

Contribution

It introduces a novel model where MOR and CI form a heteromer complex in solution, enhancing switch robustness, which aligns better with experimental data.

Findings

Heteromer formation in cytoplasm best explains experimental repression data.

Cytoplasmic MOR:CI complexes sequester CI, increasing switch stability.

Model predicts bistability consistent with observed phage behavior.

Abstract

The lytic-lysogenic switch of the temperate lactococcal phage TP901-1 is fundamentally different from that of phage lambda. In phage TP901-1, the lytic promoter PL is repressed by CI whereas repression of the lysogenic promoter PR requires the presence of both of the antagonistic regulator proteins, MOR and CI. We model the central part of the switch and compare the two cases for PR repression: the one where the two regulators interact only on the DNA, and the other where the two regulators form a heteromer complex in the cytoplasm prior to DNA binding. The models are analyzed for bistability, and the predicted promoter repression folds are compared to experimental data. We conclude that the experimental data are best reproduced the latter case, where a heteromer complex forms in solution. We further find that CI sequestration by the formation of MOR:CI complexes in cytoplasm makes the genetic switch robust.