Universität zu Köln

Zhang, Ming ORCID: 0000-0001-8425-2245, Chen, Jeffrey M., Sala, Claudia ORCID: 0000-0003-4031-4648, Rybniker, Jan, Dhar, Neeraj ORCID: 0000-0002-5887-8137 and Cole, Stewart T. (2014). EspI regulates the ESX-1 secretion system in response to ATP levels in Mycobacterium tuberculosis. Mol. Microbiol., 93 (5). S. 1057 - 1066. HOBOKEN: WILEY-BLACKWELL. ISSN 1365-2958

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Abstract

The function of EspI, a 70kDa 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. tuberculosisEspI 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zhang, Ming UNSPECIFIED orcid.org/0000-0001-8425-2245 UNSPECIFIED Chen, Jeffrey M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sala, Claudia UNSPECIFIED orcid.org/0000-0003-4031-4648 UNSPECIFIED Rybniker, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Dhar, Neeraj UNSPECIFIED orcid.org/0000-0002-5887-8137 UNSPECIFIED Cole, Stewart T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-431316
DOI:	10.1111/mmi.12718
Journal or Publication Title:	Mol. Microbiol.
Volume:	93
Number:	5
Page Range:	S. 1057 - 1066
Date:	2014
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1365-2958
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COMPLETE GENOME SEQUENCE; CALMETTE-GUERIN; VIRULENCE; ATTENUATION; PROTEINS; TRANSFORMATION; BIOSYNTHESIS; DORMANCY; SYNTHASE; BACILLUS Multiple languages Biochemistry & Molecular Biology; Microbiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43131