Metabolic cross-feeding interactions are ubiquitous in natural microbial communities. However, it remains generally unclear whether the production and exchange of metabolites incurs fitness costs to the producing cells and if so, which ecological mechanisms can facilitate a cooperative exchange of metabolites among unrelated individuals. We hypothesized that positive assortment within structured environments can maintain mutualistic cross-feeding. To test this, we engineered Acinetobacter baylyi and Escherichia coli to reciprocally exchange essential amino acids. Interspecific coculture experiments confirmed that non-cooperating types were selectively favoured in spatially unstructured (liquid culture), yet disfavoured in spatially structured environments (agar plates). Both an individual-based model and experiments with engineered genotypes indicated that a segregation of cross-feeders and non-cooperating auxotrophs stabilized cooperative cross-feeding in spatially structured environments. Chemical imaging confirmed that auxotrophs were spatially excluded from cooperative benefits. Together, these results demonstrate that cooperative crossfeeding between different bacterial species is favoured in structured environments such as bacterial biofilms, suggesting this type of interactions might be common in natural bacterial communities.

Bacterial communities are taxonomically highly diverse, yet the mechanisms that maintain this diversity remain poorly understood. We hypothesized that an obligate and mutual exchange of metabolites, as is very common among bacterial cells, could stabilize different genotypes within microbial communities. To test this, we developed a cellular automaton to model interactions among six empirically characterized genotypes that differ in their ability and propensity to produce amino acids. By systematically varying intrinsic (i.e. benefit-to-cost ratio) and extrinsic parameters (i.e. metabolite diffusion level, environmental amino acid availability), we show that obligate cross-feeding of essential metabolites is selected for under a broad range of conditions. In spatially structured environments, positive assortment among cross-feeders resulted in the formation of cooperative clusters, which limited exploitation by non-producing auxotrophs, yet allowed them to persist at the clusters’ periphery. Strikingly, cross-feeding helped to maintain genotypic diversity within populations, while amino acid supplementation to the environment decoupled obligate interactions and favored auxotrophic cells that saved amino acid production costs over metabolically autonomous prototrophs. Together, our results suggest that spatially structured environments and limited nutrient availabilities should facilitate the evolution of metabolic interactions, which can help to maintain genotypic diversity within natural microbial populations.

The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given.

Opportunistic human pathogenic fungi like the ubiquitous fungus Aspergillus fumigatus are a major threat to immunocompromised patients. An impaired immune system renders the body vulnerable to invasive mycoses that often lead to the death of the patient. While the number of immunocompromised patients is rising with medical progress, the process, and dynamics of defense against invaded and ready to germinate fungal conidia are still insufficiently understood. Besides macrophages, neutrophil granulocytes form an important line of defense in that they clear conidia. Live imaging shows the interaction of those phagocytes and conidia as a dynamic process of touching, dragging, and phagocytosis. To unravel strategies of phagocytes on the hunt for conidia an agent-based modeling approach is used, implemented in NetLogo. Different modes of movement of phagocytes are tested regarding their clearing efficiency: random walk, short-term persistence in their recent direction, chemotaxis of chemokines excreted by conidia, and communication between phagocytes. While the short-term persistence hunting strategy turned out to be superior to the simple random walk, following a gradient of chemokines released by conidial agents is even better. The advantage of communication between neutrophilic agents showed a strong dependency on the spatial scale of the focused area and the distribution of the pathogens.

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