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Jeff Green, Department of Molecular Biology and Biotechnology, University of Sheffield, presents this Plant and Microbial Sciences Research Seminar on; “Cyclic AMP and Nitric Oxide Responsive Gene Regulatory Circuits in Mycobacterium tuberculosis.”

Abstract: Mycobacterium tuberculosis is a major cause of human mortality and morbidity.  Approximately one third of the world’s population is infected and, as the causative agent of tuberculosis.  Most infected individuals are essentially asymptomatic, a state characterized by the presence of M. tuberculosis in a persistent non-replicating state.  However, 1 in 10 infected individuals will become ill with active tuberculosis during their lifetimes.  Establishing and emerging from the persistent state are processes rooted in reprogramming gene expression.  The M. tuberculosis cyclic AMP receptor protein Rv3676 is a global regulator that is required for virulence.  Amongst the genes regulated by Rv3676 are rpfA, whiB1 and espA.  This is of interest because rpfA encodes a protein that is thought to be involved in reviving dormant bacteria, whiB1 encodes a member of a family of proteins (Wbl) that are involved in developmental processes in Actinomycetes, and EspA is an essential component of the ESX-1 protein secretion machinery.  The seminar will: (1) establish the importance of cAMP signaling in M. tuberculosis and show how Rv3676 has adapted to operate against a background of relatively high cAMP concentrations; (2) provide evidence to show that WhiB1 is an essential nitric oxide responsive regulator of gene expression; and (3) link sensing of cAMP and nitric oxide to regulation of the key virulence component ESAT-6

For more information please contact Alexander Grabov