title: EspD is critical for the virulence-mediating ESX-1 secretion system in Mycobacterium tuberculosis.
abstract: ESAT-6 system 1 (ESX-1)-mediated secretion in Mycobacterium tuberculosis is dependent on proteins encoded by the cotranscribed espA-espC-espD gene cluster. While the roles of EspA and EspC with respect to the ESX-1 secretion system have been actively investigated, the function of EspD remains unknown. We show that EspD is secreted by M. tuberculosis, but unlike EspA and EsxA, its export does not exclusively require the ESX-1 system. Evidence for stabilization of cellular levels of EspA and EspC by EspD is presented, and depletion of EspD results in loss of EsxA secretion. Site-directed mutagenesis of EspD reveals that its role in the maintenance of cellular levels of EspA in M. tuberculosis is distinct from its facilitation of EsxA secretion. The same mutagenesis experiments have also shown that secretion of EspD is not required for the secretion of EsxA. Our findings highlight a critical and complex role for EspD in modulating the ESX-1 secretion system in M. tuberculosis.
authors.affiliation: École Polytechnique Fédérale de Lausanne, Global Health Institute, Lausanne, Switzerland.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Chen
authors.forename: Stefanie
authors.initials: S
authors.lastname: Boy-Röttger
authors.forename: Neeraj
authors.initials: N
authors.lastname: Dhar
authors.forename: Nathan
authors.initials: N
authors.lastname: Sweeney
authors.forename: Roger S
authors.initials: RS
authors.lastname: Buxton
authors.forename: Florence
authors.initials: F
authors.lastname: Pojer
authors.forename: Ida
authors.initials: I
authors.lastname: Rosenkrands
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D015398:Signal Transduction
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C093276:ESAT-6 protein, Mycobacterium tuberculosis