Cobra Vs Predator: A Chance for Multi-Scale Modeling of the Microbial Prey-Predator Relationship

Predation is a type of interspecific interaction broadly extended in nature in which an individual (the predator) feeds on another (the prey) to survive. Interspecific relationships are interesting from the ecological and evolutionary point of view, since interactions between organisms have played a key role in the diversification and organization of life (Thompson, 1999). Bdellovibrio bacteriovorus HD100 is a small, highly motile deltaproteobacterium that preys upon a wide variety of other Gram-negative bacteria. This predator exhibits a biphasic growth cycle, including a free-swimming attack phase (AP) and an intraperiplasmic growth phase (GP). The AP is characterized by restricted nutrient conditions while the predator searches for new preys to penetrate. Once Bdellovibrioenters in the prey`s periplasm, it replicates its DNA during the GP and, by means of its large array of hydrolytic enzymes, it grows using the prey as source of nutrients and biomass building blocks (Sockett, 2009). Therefore, this life cycle is subjected to both nutrient availability and biological function.

Constraint-based Reconstruction and Analysis (COBRA) methods have provided important insights into genotype-phenotype relationship of single living systems. Recently, COBRA approaches have been applied for better understanding of interspecies interactions such as mutualism, competition and parasitism (Lewis et al., 2012). In order to expand our knowledge regarding the microbial interspecies relationship at system level, here, we present a new case of multi-scale modeling through an integrative framework. By combining genome-scale metabolic modeling with available high-throughput omics and physiological data, we successfully address the predatory interspecific relationship.

We have constructed a full compartmented, mass and charge balanced genome-scale metabolic model of B. bacteriovorus (iCH457) which possesses 457 genes, 996 reactions and 949 metabolites distributed into 30 metabolic subsystems. During the reconstruction process we found numerous incomplete biosynthetic pathways suggesting a large amount of auxotrophies which could drive its obligatory predatory lifestyle. Consequently, the model was used to define the minimal medium supporting growth. Our results were further validated by growth and ATP production rates predictions in several carbon sources showing good agreement with the experimental data.

The metabolic shifts during the dual life cycle of Bdellovibrio were investigated by constructing condition-specific models integrating available gene expression data from the two states of Bdellovibrio growth cycle (AP and GP) (Karunker et al., 2013) within iCH457. The solution spaces from these condition-specific models were systematically compared by random sampling. In the AP, we noticed the carbon flux mainly directed to ATP production and the absence of biosynthetic fluxes, while flux distribution in GP resembled classical heterotrophic metabolism.

For a deeper understanding of the predator-prey interaction and taking advantage of the high-quality metabolic models of Escherichia coli (iJO1366) and Pseudomonas putida (iJN1411), we aim to perform a multi-scale modeling to simulate the predation process on these two in silico strains. This approach would allow us to obtain new insights into microbial interspecific relationships that will be discussed within the context of predation scenarios, its evolutionary and biotechnological perspectives.