%0 Journal Article
%T A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2
%A Ines Thiele
%A Daniel R Hyduke
%A Benjamin Steeb
%A Guy Fankam
%A Douglas K Allen
%A Susanna Bazzani
%A Pep Charusanti
%A Feng-Chi Chen
%A Ronan MT Fleming
%A Chao A Hsiung
%A Sigrid CJ De Keersmaecker
%A Yu-Chieh Liao
%A Kathleen Marchal
%A Monica L Mo
%A Emre £¿zdemir
%A Anu Raghunathan
%A Jennifer L Reed
%A Sook-Il Shin
%A Sara Sigurbj£¿rnsd¨®ttir
%A Jonas Steinmann
%A Suresh Sudarsan
%A Neil Swainston
%A Inge M Thijs
%A Karsten Zengler
%A Bernhard O Palsson
%A Joshua N Adkins
%A Dirk Bumann
%J BMC Systems Biology
%D 2011
%I BioMed Central
%R 10.1186/1752-0509-5-8
%X Here, we describe a community-driven effort, in which more than 20 experts in S. Typhimurium biology and systems biology collaborated to reconcile and expand the S. Typhimurium BiGG knowledge-base. The consensus MR was obtained starting from two independently developed MRs for S. Typhimurium. Key results of this reconstruction jamboree include i) development and implementation of a community-based workflow for MR annotation and reconciliation; ii) incorporation of thermodynamic information; and iii) use of the consensus MR to identify potential multi-target drug therapy approaches.Taken together, with the growing number of parallel MRs a structured, community-driven approach will be necessary to maximize quality while increasing adoption of MRs in experimental design and interpretation.The evolution of antibiotic resistance by a variety of human pathogens is a looming public health threat [1,2]. Salmonella is a major human pathogen and a model organism for bacterial pathogenesis research [3]. S. enterica subspecies I serovar Typhimurium (S. Typhimurium) is the principle subspecies employed in molecular biology and its variants are causative agents in gastroenteritis in humans. The publication of the annotated genome for S. Typhimurium LT2 provided a foundation for numerous applications, such as drug discovery [4]. Previous efforts to systematically identify candidate drug targets within metabolism did not result in a plethora of new candidates, due to the robustness and redundancy of S. Typhimurium's metabolic network [5]. Since new single protein targets are missing, we need to target multiple proteins conjointly. Unfortunately, antibiotic regimens, which require multiple targets to be hit simultaneously, have an increased probability of the pathogen evolving resistance relative to a single target therapy. However, the continuous clinical success of the combination of beta-lactams and beta-lactamase inhibitors actually demonstrates that inhibitor combinations can b
%U http://www.biomedcentral.com/1752-0509/5/8