Dataset Information

Label-free quantitative proteomics reveals a role for the Mycobacterium tuberculosis SecA2 pathway in exporting solute binding proteins and Mce transporters to the cell wall

ABSTRACT: Mycobacterium tuberculosis is an example of a bacterial pathogen with a specialized SecA2-dependent protein export system that contributes to its virulence. Our understanding of the mechanistic basis of SecA2-dependent export and the role(s) of the SecA2 pathway in M. tuberculosis pathogenesis has been hindered by our limited knowledge of the proteins exported by the pathway. Here, we set out to identify M. tuberculosis proteins that use the SecA2 pathway for their export from the bacterial cytoplasm to the cell wall. Using label-free quantitative (LFQ) proteomics involving spectral counting, we compared the cell wall and cytoplasmic proteomes of wild type M. tuberculosis to that of a ΔsecA2 mutant. This work revealed a role for the M. tuberculosis SecA2 pathway in the cell wall localization of solute binding proteins (SBPs) that work with ABC transporters to import solutes. Another discovery was a profound effect of SecA2 on the cell wall localization of the Mce1 and Mce4 lipid transporters, which contribute to M. tuberculosis virulence. In addition to the effects on SBP and Mce transporter export, our LFQ analysis revealed an unexpected relationship between SecA2 and the hypoxia-induced DosR regulon, which is associated with M. tuberculosis latency. Nearly half of the transcriptionally controlled DosR regulon of cytoplasmic proteins were detected at higher levels in the ΔsecA2 mutant versus wild type M. tuberculosis. By increasing the list of M. tuberculosis proteins known to be affected by the SecA2 pathway, this study expands our appreciation of the types of proteins exported by this pathway and guides our understanding of the mechanism of SecA2-dependent protein export in mycobacteria. At the same time, the newly identified SecA2-dependent proteins are helpful for understanding the significance of this pathway to M. tuberculosis virulence and physiology

INSTRUMENT(S):

ORGANISM(S): Mycobacterium Tuberculosis H37rvae

SUBMITTER: Kate Zulauf

LAB HEAD: Miriam Braunstein

PROVIDER: PXD002144 | Pride | 2018-10-24

REPOSITORIES: Pride

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Label-free Quantitative Proteomics Reveals a Role for the Mycobacterium tuberculosis SecA2 Pathway in Exporting Solute Binding Proteins and Mce Transporters to the Cell Wall.

Feltcher Meghan E ME Gunawardena Harsha P HP Zulauf Katelyn E KE Malik Seidu S Griffin Jennifer E JE Sassetti Christopher M CM Chen Xian X Braunstein Miriam M

Molecular & cellular proteomics : MCP 20150326 6

Mycobacterium tuberculosis is an example of a bacterial pathogen with a specialized SecA2-dependent protein export system that contributes to its virulence. Our understanding of the mechanistic basis of SecA2-dependent export and the role(s) of the SecA2 pathway in M. tuberculosis pathogenesis has been hindered by our limited knowledge of the proteins exported by the pathway. Here, we set out to identify M. tuberculosis proteins that use the SecA2 pathway for their export from the bacterial cyto ...[more]

PMID: 25813378

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			Action	DRS
	F023587.dat	Other
	F026460.dat	Other
	MU_A1.mzML	Mzml
	MU_A10.mzML	Mzml
	MU_A11.mzML	Mzml