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Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18792-7. doi: 10.1073/pnas.0900589106. Epub 2009 Oct 21.

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

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Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.


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.

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