Boolean Models of Biosurfactants Production in Pseudomonas fluorescens

Cyclolipopeptides (CLPs) are biosurfactants produced by numerous Pseudomonas fluorescens strains. CLP production is known to be regulated at least by the GacA/GacS two-component pathway, but the full regulatory network is yet largely unknown. In the clinical strain MFN1032, CLP production is abolished by a mutation in the phospholipase C gene () and not restored by complementation. Their production is also subject to phenotypic variation. We used a modelling approach with Boolean networks, which takes into account all these observations concerning CLP production without any assumption on the topology of the considered network. Intensive computation yielded numerous models that satisfy these properties. All models minimizing the number of components point to a bistability in CLP production, which requires the presence of a yet unknown key self-inducible regulator. Furthermore, all suggest that a set of yet unexplained phenotypic variants might also be due to this epigenetic switch. The simplest of these Boolean networks was used to propose a biological regulatory network for CLP production. This modelling approach has allowed a possible regulation to be unravelled and an unusual behaviour of CLP production in P. fluorescens to be explained

Summary of experimental results concerning the production of hemolytic activity, phospholipase C and cyclolipopeptides in different genetic backgrounds.

<p>: Presence; : Absence (early stationary growth phase in LB medium at C).</p

Hypothetic biological regulatory network of CLP production (with negative interactions) deduced from the Boolean model.

<p>Circles represent the proteins in the network and edges represent regulatory interaction (bold lines: known interactions, dotted lines: hypothetical interactions). Arrow headed edges represent positive regulatory interaction, and T-headed edges represent negative interaction. PlcC: phospholipase C; CLPs: cyclolipopeptides production; R: unknown regulator (with positive feedback).</p

The two minimal consistent Boolean networks with 3 components.

<p>The graphical conventions used to described the interaction graph of each network are as follows: normal arrows correspond to positive interactions, and T-end arrows correspond to negative interactions. Asynchronous state graphs are represented in a 3D-grid, with in the vertical axis (first component), in the horizontal axis (second component), and in the third axis (third component).</p