Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition
Siegrist, M. Sloan; Steigedal, Magnus; Ahmad, Rushdy; Mehra, Alka; Dragset, Marte Singsås; Schuster, Brian M.; Phillips, Jennifer A.; Carr, Steven A.; Rubin, Eric J
Journal article, Peer reviewed
Published version
Permanent lenke
http://hdl.handle.net/11250/2449958Utgivelsesdato
2014Metadata
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Originalversjon
10.1128/mBio.01073-14Sammendrag
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.