ABSTRACT
The dynamic modelling of metabolic networks aims to describe the temporal evolution of metabolite concentrations in cells. This area has attracted increasing attention in recent years owing to the availability of high-throughput data and the general development of systems biology as a promising approach to study living organisms. Biochemical Systems Theory (BST) provides an accurate formalism to describe biological dynamic phenomena. However, knowledge about the molecular organization level, used in these models, is not enough to explain phenomena such as the driving forces of these metabolic networks. Dynamic Energy Budget (DEB) theory captures the quantitative aspects of the organization of metabolism at the organism level in a way that is non-species-specific. This imposes constraints on the sub-organismal organization that are not present in the bottom-up approach of systems biology. We use in vivo data of lactic acid bacteria under various conditions to compare some aspects of BST and DEB approaches. Due to the large number of parameters to be estimated in the BST model, we applied powerful parameter identification techniques. Both models fitted equally well, but the BST model employs more parameters. The DEB model uses similarities of processes under growth and no-growth conditions and under aerobic and anaerobic conditions, which reduce the number of parameters. This paper discusses some future directions for the integration of knowledge from these two rich and promising areas, working top-down and bottom-up simultaneously. This middle-out approach is expected to bring new ideas and insights to both areas in terms of describing how living organisms operate.
Subject(s)
Energy Metabolism , Metabolic Networks and Pathways , Models, Biological , Lactobacillus/metabolismABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) isolates have previously been classified into major epidemic clonal types by pulsed-field gel electrophoresis in combination with multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec typing. We aimed to investigate whether genetic variability in potentially polymorphic domains of virulence-related factors could provide another level of differentiation in a diverse collection of epidemic MRSA clones. The target regions of strains representative of epidemic clones and genetically related methicillin-susceptible S. aureus isolates from the 1960s that were sequenced included the R domains of clfA and clfB; the D, W, and M regions of fnbA and fnbB; and three regions in the agr operon. Sequence variation ranged from very conserved regions, such as those for RNAIII and the agr interpromoter region, to the highly polymorphic R regions of the clf genes. The sequences of the clf R domains could be grouped into six major sequence types on the basis of the sequences in their 3' regions. Six sequence types were also observed for the fnb sequences at the amino acid level. From an evolutionary point of view, it was interesting that a small DNA stretch at the 3' clf R-domain sequence and the fnb sequences agreed with the results of MLST for this set of strains. In particular, clfB R-domain sequences, which had a high discriminatory capacity and with which the types distinguished were congruent with those obtained by other molecular typing methods, have potential for use for the typing of S. aureus. Clone- and strain-specific sequence motifs in the clf and fnb genes may represent useful additions to a typing methodology with a DNA array.
