Application of Metabolic Network Models to Develop New Preservation Strategies: An Industrial Perspective

The development of omics technologies and systems biology provides new opportunities to design novel strategies for antimicrobial intervention in the food chain. Among the systems approaches of interest, genome-scale metabolic models (GSMMs) provide a biologically meaningful mechanistic basis for elucidating the genotype-phenotype relationship. GSMMs contain curated and systematized information about known metabolites and metabolic reactions of a given bacterial cell. GSMMs have been used in a number of applications, including the discovery of drug targets. The method consists in simulating gene knockouts to identifying genes that could be targeted to prevent bacterial growth. However, little or no application of GSMMs to support the design of preservation strategies to control bacterial growth in consumer products has been reported. It is expected that incorporating specific information on the metabolism of the bacterial cell exposed to preservatives in the GSMMs would facilitate this application.

We present two case studies that demonstrate the potential of GSMMs to design novel antimicrobial strategies in an industrial context. The first study involves using light-emitting luciferase biosensor mutants in combination with GSMM modelling as a novel approach to identify key genes/pathways (either cellular targets of the preservatives or resistance pathways). Light-emitting mutants corresponding to the selected genes can be assembled in biosensor panels and be used to identify optimized combinations of preservatives. The second study focuses on developing metabolic models that are specific to the cell metabolism under the action of the selected preservatives. This can be achieved by mapping expression data and metabolomics profiles of bacteria exposed to selected preservatives onto the GSMMs. Gene(s) deletion analysis will then allow identifying targets that can specially potentiate the efficacy of the antibacterial treatment. Note that the benefit that this second study can bring to the industry will also depend on our ability to find compounds that can inhibit the identified cellular targets.