X-ray crystallography; Type VII secretion system; Mycobacterium tuberculosis
Chen JM, Boy-Rottger S, Dhar N, Sweeney N, Buxton RS, Pojer F, Rosenkrands I, Cole ST (2012), EspD Is Critical for the Virulence-Mediating ESX-1 Secretion System in Mycobacterium tuberculosis, in JOURNAL OF BACTERIOLOGY
, 194(4), 884-893.
Blasco B, Stenta M, Alonso-Sarduy L, Dietler G, Dal Peraro M, Cole ST, Pojer F (2011), Atypical DNA recognition mechanism used by the EspR virulence regulator of Mycobacterium tuberculosis, in MOLECULAR MICROBIOLOGY
, 82(1), 251-264.
Chen J.M. Pojer F.* Blasco B.and Cole S.T. (2010), Towards anti-virulence drugs targeting ESX-1 mediated pathogenesis of Mycobacterium tuberculosis, in Drug Discovery Today – Disease Mechanisms
, 7(1), e25-e31.
The recently identified type VII secretion systems (T7SS) are found in various Gram-positive bacteria, pathogenic or not, and probably play a general role in bacterial homeostasis and cell-to-cell communication. However, T7SS do play important roles in pathogenesis, e.g. in the human pathogens Mycobacterium tuberculosis (M. tb) by secreting virulence factors into the host cells. T7SS are encoded by conserved gene clusters comprising approximately 20 open reading frames, which contain genes coding for the core components of T7SS, for accessory proteins and secreted proteins. Five T7SSs clusters are present in M. tb, one of them, ESX-1 being the major virulence determinant, which has been lost in the vaccine strain M. bovis BCG. My host laboratory is a world leader in tuberculosis (TB) research aiming to discover and develop new drugs for the treatment of TB through an integrated approach. We propose to use protein X-ray crystallography coupled to biochemical analysis to establish the organization, architecture and function of this newly discovered T7 secretory apparatus, which represents a potential target for new classes of TB drugs.