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


In this project we propose to study the relation between the cell cycle and dormancy development in Mycobacterium tuberculosis (Mtb).
The final aim is to increase the knowledge on dormancy development and to identify potential candidates for the development of antitubercular drugs specifically active in dormant bacilli. Mtb is a facultative intracellular pathogen able to infect the human lung for decades without showing any symptom. Following immunity suppression caused by age, diseases, or malnutrition, tubercle bacilli can reactivate to give overt disease.
About one third of the human population is estimated to be affected by latent tuberculosis representing a huge reservoire for the infection. The lack of drugs efficiently active on dormant bacteria is a major problem in fighting this important disease.
Conditional mutants unable to express important cell cycle regulators will be constructed and used to study their role in
i) global regulation of gene expression; ii) cell cycle proteins cytolocalization;
iii) latency development in vitro and in vivo.
Additionally, a transposon insertion library will be used to identify new mycobacterial genes essential for survival to prolonged stationary phase, and their expression will be measured during progressive and latent infection.

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Via 8 Febbraio, 2

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