EspI regulates the ESX‐1 secretion system in response to ATP levels in Mycobacterium tuberculosis. Issue 5 (31st July 2014)

• Record Type: Journal Article
• Authors: Zhang, Ming; Chen, Jeffrey M.; Sala, Claudia; Rybniker, Jan; Dhar, Neeraj; Cole, Stewart T.
• Is Part Of: Molecular microbiology. Volume 93:Issue 5(2014)
• Page Start: 1057
• Page End: 1065
• Publication Date: 2014-07-31
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12718
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>The function of EspI, a 70 kDa protein in <italic>M</italic><italic>ycobacterium tuberculosis</italic>, has remained unclear. Although EspI is encoded by a gene within the <italic>esx‐1</italic> locus, in this study we clarify previous conflicting results and show that EspI is not essential for ESX‐1‐mediated secretion or virulence in <italic>M</italic><italic>. tuberculosis</italic>. We also provide evidence that reduction of cellular ATP levels in wild‐type <italic>M</italic><italic>. tuberculosis</italic> using the drug bedaquiline completely blocks ESX‐1‐mediated secretion. Remarkably, <italic>M</italic><italic>. tuberculosis</italic> lacking EspI fails to exhibit this phenotype. Furthermore, mutagenesis of a highly conserved ATP‐binding motif in EspI renders <italic>M</italic><italic>. tuberculosis</italic> incapable of shutting down ESX‐1‐mediated secretion during ATP depletion. Collectively these results show that <italic>M</italic><italic>. tuberculosis</italic> 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.</p> </abstract>