Applications of system-level models of metabolism for analysis of bacterial physiology and identification of new drug targets

Abstract

For nearly all of the 20th century, biologists gained considerable insights into the fundamental principles of cellular dynamics by examining select modules of biochemical processes. This form of analysis provides detailed information about the workings of the examined pathways. However, any attempt to alter the normal function of bacteria (perhaps for industrial or medicinal goals) requires a detailed global understanding of cellular mechanisms. The reductionist mode of analysis cannot provide the required information for developing the needed perspective on the complex interactions of biochemical pathways. Thankfully, the increasing availability of microbial genomic, transcriptomic, proteomic and other high-throughput data permits system-level analyses of microbiology. During the past two decades, systems biologists have developed constraint-based genome-scale models (GSM) of metabolism for a variety of pathogens. These models are important tools for assessing the metabolic capabilities of various genotypes. Simultaneously, new computational methods have been developed that use these network reconstructions to answer an array of important immunological questions. The objective of this article is to briefly review some of the uses of GSMs for studying bacterial metabolism under different conditions and to discuss how the calculated solutions can be used for rational design of drugs. © The Author 2011. Published by Oxford University Press.