Interaction networks for identifying coupled molecular processes in microbial communities

Magnus Bosse, Alexander Heuwieser, Andreas Heinzel, Ivan Nancucheo, Hivana Melo Barbosa Dall’Agnol, Arno Lukas, George Tzotzos, Bernd Mayer

Microbial communities adapt to environmental conditions for optimizing metabolic flux. Such adaption may include cooperative mechanisms eventually resulting in phenotypic observables as emergent properties that cannot be attributed to an individual species alone. Understanding the molecular basis of cross-species cooperation adds to utilization of microbial communities in industrial applications including metal bioleaching and bioremediation processes. With significant advancements in metagenomics the composition of microbial communities became amenable for integrative analysis on the level of entangled molecular processes involving more than one species, in turn offering a data matrix for analyzing the molecular basis of cooperative phenomena. We present an analysis framework aligned with a dynamical hierarchies concept for unraveling emergent properties in microbial communities, and exemplify this approach for a co-culture setting of At. ferrooxidans and At. thiooxidans. This minimum microbial community demonstrates a significant increase in bioleaching efficiency compared to the activity of individual species, involving mechanisms of the thiosulfate, the polysulfide and the iron oxidation pathway. Populating gene-centric data structures holding rich functional annotation and interaction information allows deriving network models at the functional level coupling energy production and transport processes of both microbial species. Applying a network segmentation approach on the interaction network of ortholog genes covering energy production and transport proposes a set of specific molecular processes of relevance in bioleaching. The resulting molecular process model essentially involves functionalities such as iron oxidation, nitrogen metabolism and proton transport, complemented by sulfur oxidation and nitrogen metabolism, as well as a set of ion transporter functionalities. At. ferrooxidans-specific genes embedded in the molecular model representation hold gene functions supportive for ammonia utilization as well as for biofilm formation, resembling key elements for effective chalcopyrite bioleaching as emergent property in the co-culture situation. Analyzing the entangled molecular processes of a microbial community on the level of segmented, gene-centric interaction networks allows identification of core molecular processes and functionalities adding to our mechanistic understanding of emergent properties of microbial consortia.