Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition
Author(s)
Siegrist, M. Sloan; Steigedal, Magnus; Ahmad, Rushdy; Mehra, Alka; Dragset, Marte S.; Schuster, Brian M.; Philips, Jennifer A.; Rubin, Eric J.; Carr, Steven A; ... Show more Show less
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The type VII secretion systems are conserved across mycobacterial species and in many Gram-positive bacteria. While the well-characterized Esx-1 pathway is required for the virulence of pathogenic mycobacteria and conjugation in the model organism Mycobacterium smegmatis, Esx-3 contributes to mycobactin-mediated iron acquisition in these bacteria. Here we show that several Esx-3 components are individually required for function under low-iron conditions but that at least one, the membrane-bound protease MycP3 of M. smegmatis, is partially expendable. All of the esx-3 mutants tested, including the ΔmycP3ms mutant, failed to export the native Esx-3 substrates EsxHms and EsxGms to quantifiable levels, as determined by targeted mass spectrometry. Although we were able to restore low-iron growth to the esx-3 mutants by genetic complementation, we found a wide range of complementation levels for protein export. Indeed, minute quantities of extracellular EsxHms and EsxGms were sufficient for iron acquisition under our experimental conditions. The apparent separation of Esx-3 function in iron acquisition from robust EsxGms and EsxHms secretion in the ΔmycP3ms mutant and in some of the complemented esx-3 mutants compels reexamination of the structure-function relationships for type VII secretion systems.
Date issued
2014-05Department
Koch Institute for Integrative Cancer Research at MITJournal
mBio
Publisher
American Society for Microbiology
Citation
Siegrist, M. S., M. Steigedal, R. Ahmad, A. Mehra, M. S. Dragset, B. M. Schuster, J. A. Philips, S. A. Carr, and E. J. Rubin. “Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition.” mBio 5, no. 3 (May 6, 2014): e01073–14–e01073–14.
Version: Final published version
ISSN
2150-7511