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      A curated C. difficile strain 630 metabolic network: prediction of essential targets and inhibitors

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      bioRxiv

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          Abstract

          Clostridium difficileis the leading cause of hospital-borne infections occurring when the natural intestinal flora is depleted following antibiotic treatment. We present iMLTC804cdf, an extensively curated reconstructed metabolic network for the C. difficilepathogenic strain 630. iMLTC804cdf contains 804 genes, 705 metabolites and 766 metabolic, 145 exchange and 118 transport reactions. iMLTC804cdf is the most complete and accurate metabolic reconstruction of a gram-positive anaerobic bacteria to date. We validate the model with simulated growth assays in different media and carbon sources and use it to predict essential genes. We obtain 88.8% accuracy in the prediction of gene essentiality when compared to experimental data for B. subtilishomologs. We predict the existence of 83 essential genes and 68 essential gene pairs, a number of which are unique to C. difficileand have non-existing or predicted non-essential human homologs. For 19 of these potential therapeutic targets, we find 72 inhibitors of homologous proteins that could serve as starting points in the development of new antibiotics, including approved drugs with the potential for drug repositioning.

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          Author and article information

          Journal
          bioRxiv
          July 09 2014
          Article
          10.1101/006932
          2d786fa1-4eb4-4ba0-8750-cbace596d7ac
          © 2014
          History

          Quantitative & Systems biology
          Quantitative & Systems biology

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