title: EspI regulates the ESX-1 secretion system in response to ATP levels in Mycobacterium tuberculosis.
abstract: The function of EspI, a 70 kDa protein in Mycobacterium tuberculosis, has remained unclear. Although EspI is encoded by a gene within the esx-1 locus, in this study we clarify previous conflicting results and show that EspI is not essential for ESX-1-mediated secretion or virulence in M. tuberculosis. We also provide evidence that reduction of cellular ATP levels in wild-type M. tuberculosis using the drug bedaquiline completely blocks ESX-1-mediated secretion. Remarkably, M. tuberculosis lacking EspI fails to exhibit this phenotype. Furthermore, mutagenesis of a highly conserved ATP-binding motif in EspI renders M. tuberculosis incapable of shutting down ESX-1-mediated secretion during ATP depletion. Collectively these results show that M. tuberculosis EspI negatively regulates the ESX-1 secretion system in response to low cellular ATP levels and this function requires the ATP-binding motif. In light of our results the potential significance of EspI in ESX-1 function during latent tuberculosis infection and reactivation is also discussed.
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Global Health Institute, Station 19, CH-1015, Lausanne, Switzerland.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Global Health Institute, Station 19, CH-1015, Lausanne, Switzerland.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Chen
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Global Health Institute, Station 19, CH-1015, Lausanne, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sala
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Global Health Institute, Station 19, CH-1015, Lausanne, Switzerland.|1 Department of Internal Medicine, University of Cologne, D-50937 Cologne, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rybniker
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Global Health Institute, Station 19, CH-1015, Lausanne, Switzerland.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Dhar
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Global Health Institute, Station 19, CH-1015, Lausanne, Switzerland.
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D000255:Adenosine Triphosphate