By using a comparative systems biology approach, the goal of this project is to develop understandable models of the metabolism of four different species of lactic acid bacteria (LAB). The central principle is that important aspects of the functional differences between organisms derive not only from the differences in genetic components but also from the interactions between their components. Comparative analyses allow detailed insight in the importance of such interactions, but also allow knowledge transfer. The so-called ”omics”-techniques (”genomics”, ”proteomics”, ”transcriptomics”, ”metabolomics”) and mathematical and statistical methods are of crucial importance.
SysMO-LAB1, the first part of this project, focused on three relatively simple and highly related LAB, which exhibit important differences in their functional relationship with humans: Lactococcus lactis, the major microorganism used in the dairy industry; Enterococcus faecalis, a major LAB in the human intestinal microbiota and a fecal contaminant in food and water as well as a contributor to food fermentation; and Streptococcus pyogenes, an important human pathogen. These organisms have a similar primary metabolism but persist in completely different environments (milk, feces, skin/mucous membranes/blood). The major regulatory events at the genetic level, the transcription, translation, enzymatic and metabolic level up to the functional level, is quantified and then integrated in iterations between experimentation (all~omics) and modeling (network structure, flux balances, dynamics, control, regulation). The SysMO-LAB1 consortium developed and applied comparative systems biology, based on the hypothesis that important aspects of phenotypic differences are related to the interaction between components, not just their presence or absence. For SysMO-LAB2, the industrially important species Lactobacillus plantarum was included. This was initiated by Nofima, as we have been working with this species in several previous research projects. L. plantarum is found in various environments including plant and meat fermentations, and in the human intestinal tract. It is associated with positive health effects (probiotic). In addition to the comparative analyses between the four species, in SysMO-LAB2 we also focus on diversity and differences within each of the species at the strain level.