Open AccessEspD Is Critical for the Virulence-Mediating ESX-1 Secretion System in Mycobacterium tuberculosis
Author(s) -
Jeffrey M. Chen,
Stefanie BoyRöttger,
Neeraj Dhar,
Nathan P. Sweeney,
Roger S. Buxton,
F. Pojer,
Ida Rosenkrands,
Stewart T. Cole
Publication year - 2012
Publication title -
journal of bacteriology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.652
H-Index - 246
eISSN - 1067-8832
pISSN - 0021-9193
DOI - 10.1128/jb.06417-11
Subject(s) - secretion , biology , mycobacterium tuberculosis , type three secretion system , mutagenesis , microbiology and biotechnology , virulence , tuberculosis , mutation , genetics , gene , biochemistry , medicine , pathology
ESAT-6 system 1 (ESX-1)-mediated secretion inMycobacterium tuberculosis is dependent on proteins encoded by the cotranscribedespA-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 byM. 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 inM. 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 inM. tuberculosis .