Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition.

TitleMycobacterial Esx-3 is required for mycobactin-mediated iron acquisition.
Publication TypeJournal Article
Year of Publication2009
AuthorsM Siegrist S, Unnikrishnan M, McConnell MJ, Borowsky M, Cheng T-Y, Siddiqi N, Fortune SM, D Moody B, Rubin EJ
JournalProc Natl Acad Sci U S A
Volume106
Issue44
Pagination18792-7
Date Published2009 Nov 3
ISSN1091-6490
KeywordsAnimals, Bacterial Proteins, Genome, Bacterial, Iron, Macrophages, Mice, Mutation, Mycobacterium, Mycobacterium Infections, Oxazoles, Protein Binding, Secretory Pathway, Siderophores, Transcription, Genetic, Up-Regulation
Abstract

The Esx secretion pathway is conserved across Gram-positive bacteria. Esx-1, the best-characterized system, is required for virulence of Mycobacterium tuberculosis, although its precise function during infection remains unclear. Esx-3, a paralogous system present in all mycobacterial species, is required for growth in vitro. Here, we demonstrate that mycobacteria lacking Esx-3 are defective in acquiring iron. To compete for the limited iron available in the host and the environment, these organisms use mycobactin, high-affinity iron-binding molecules. In the absence of Esx-3, mycobacteria synthesize mycobactin but are unable to use the bound iron and are impaired severely for growth during macrophage infection. Mycobacteria thus require a specialized secretion system for acquiring iron from siderophores.

DOI10.1073/pnas.0900589106
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID19846780
PubMed Central IDPMC2774023
Grant ListR01 AI48704 / AI / NIAID NIH HHS / United States
R0171155 / / PHS HHS / United States