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Transcriptional regulation and cellular localization of mycobacterial cell cycle proteins during dormancy

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Delineating dormancy of Mycobacterium tuberculosis

Identification of the molecular determinants of Mycobacterium tuberculosis (M.tuberculosis) dormant state is the subject of many research efforts. An EU-funded project developed an assay for studying mycobacteria resistant to hypoxic conditions.

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It is estimated that about one third of the human population is infected with latent tuberculosis. However, our understanding of dormancy development of M.tuberculosis and its activation to induce disease is limited. This hampers the development of drugs that are effective against dormant bacteria. The ‘Transcriptional regulation and cellular localization of mycobacterial cell cycle proteins during dormancy’ (Mycomancy) project aimed to enhance knowledge of the M.tuberculosis life-cycle and identify drug targets. Mycomancy partners developed a series of useful tools for studying the cell cycle of M.tuberculosis and understanding the physiology of latency. Antibodies against various cell division proteins were produced and their efficiency tested in actively growing, dormant and growth-deficient bacteria. In order to identify new mycobacterial genes essential for survival to prolonged stationary phase, scientists screened a library of mutants of the non-pathogenic strain M. smegmatis. The bacteria were subjected to anaerobic conditions and those that proved resistant to hypoxia were isolated and studied. Further studies on the proteins encoded by these genes are expected to increase our knowledge of the mechanism used by mycobacteria to survive in a low-oxygen environment. They also represent good candidates for the development of drugs active against dormant bacteria.

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