title: EspC forms a filamentous structure in the cell envelope of Mycobacterium tuberculosis and impacts ESX-1 secretion.
abstract: Pathogenicity of Mycobacterium tuberculosis (M. tb) is mediated by the ESX-1 secretion system, which exports EsxA and EsxB, the major virulence factors that are co-secreted with EspA and EspC. Functional information about ESX-1 components is scarce. Here, it was shown that EspC associates with EspA in the cytoplasm and membrane, then polymerizes during secretion from M. tb. EspC was localized by immuno-gold electron microscopy in whole cells or cryosections as a surface-exposed filamentous structure that seems to span the cell envelope. Consistent with these findings, purified EspC homodimerizes via disulphide bond formation, multimerizes and self-assembles into long filaments in vitro. The C-terminal domain is required for multimerization as truncation and selected point mutations therein impact EspC filament formation, thus reducing secretion of EsxA and causing attenuation of M. tb. The data are consistent with EspC serving either as a modulator of ESX-1 function or as a component of the secretion apparatus.
authors.affiliation: Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lou
authors.affiliation: Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.|1st Department of Internal Medicine, University of Cologne, Cologne, D-50937, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rybniker
authors.affiliation: Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sala
authors.affiliation: Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D058947:Bacterial Secretion Systems / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism; D000069377:Type VII Secretion Systems / Q000235:genetics* / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D000069377:Type VII Secretion Systems; D037521:Virulence Factors