02243nas a2200169   4500008004100000022001400041245016700055210006900222260008100291300000800372490000600380520150400386100002101890700001701911700001901928856012601947       2010                        eng d  a1752-050900aSystems approach to investigating host-pathogen interactions in infections with the biothreat agent Francisella. constraints-based model of Francisella tularensis0 aSystems approach to investigating hostpathogen interactions in i  a236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLANDbBIOMED CENTRAL LTDcAUG  a1180 v43 a<p>Background: Francisella tularensis is a prototypic example of a pathogen for which few experimental datasets exist, but for which copious high-throughout data are becoming available because of its re-emerging significance as biothreat agent. The virulence of Francisella tularensis depends on its growth capabilities within a defined environmental niche of the host cell. Results: We reconstructed the metabolism of Francisella as a stoichiometric matrix. This systems biology approach demonstrated that changes in carbohydrate utilization and amino acid metabolism play a pivotal role in growth, acid resistance, and energy homeostasis during infection with Francisella. We also show how varying the expression of certain metabolic genes in different environments efficiently controls the metabolic capacity of F. tularensis. Selective gene-expression analysis showed modulation of sugar catabolism by switching from oxidative metabolism (TCA cycle) in the initial stages of infection to fatty acid oxidation and gluconeogenesis later on. Computational analysis with constraints derived from experimental data revealed a limited set of metabolic genes that are operational during infection. Conclusions: This integrated systems approach provides an important tool to understand the pathogenesis of an ill-characterized biothreat agent and to identify potential novel drug targets when rapid target identification is required should such microbes be intentionally released or become epidemic.</p>1 aRaghunathan, Anu1 aShin, Sookil1 aDaefler, Simon  uhttps://library.ncl.res.in/content/systems-approach-investigating-host-pathogen-interactions-infections-biothreat-agent-0