| http://purl.uniprot.org/citations/20305657 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20305657 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20305657 | http://www.w3.org/2000/01/rdf-schema#comment | "New chemotherapeutics are urgently required to control the tuberculosis pandemic. We describe a new pathway from trehalose to alpha-glucan in Mycobacterium tuberculosis comprising four enzymatic steps mediated by TreS, Pep2, GlgE (which has been identified as a maltosyltransferase that uses maltose 1-phosphate) and GlgB. Using traditional and chemical reverse genetics, we show that GlgE inactivation causes rapid death of M. tuberculosis in vitro and in mice through a self-poisoning accumulation of maltose 1-phosphate. Poisoning elicits pleiotropic phosphosugar-induced stress responses promoted by a self-amplifying feedback loop where trehalose-forming enzymes are upregulated. Moreover, the pathway from trehalose to alpha-glucan exhibited a synthetic lethal interaction with the glucosyltransferase Rv3032, which is involved in biosynthesis of polymethylated alpha-glucans, because key enzymes in each pathway could not be simultaneously inactivated. The unique combination of maltose 1-phosphate toxicity and gene essentiality within a synthetic lethal pathway validates GlgE as a distinct potential drug target that exploits new synergistic mechanisms to induce death in M. tuberculosis."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.org/dc/terms/identifier | "doi:10.1038/nchembio.340"xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.org/dc/terms/identifier | "doi:10.1038/nchembio.340"xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Liu Z."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Liu Z."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Jacobs W.R. Jr."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Jacobs W.R. Jr."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Sacchettini J.C."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Sacchettini J.C."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Syson K."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Syson K."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Bornemann S."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Bornemann S."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Kalscheuer R."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Kalscheuer R."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Veeraraghavan U."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Veeraraghavan U."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Weinrick B."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Weinrick B."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Besra G."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Besra G."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Biermann K.E."xsd:string |
| http://purl.uniprot.org/citations/20305657 | http://purl.uniprot.org/core/author | "Biermann K.E."xsd:string |