Siegrist, M. SloanUnnikrishnan, MeeraMcConnell, Matthew J.Borowsky, MarkCheng, Tan-YunSiddiqi, NomanFortune, Sarah M.Moody, D. BranchRubin, Eric J.2019-10-152009Siegrist, M. S., M. Unnikrishnan, M. J. McConnell, M. Borowsky, T.-Y. Cheng, N. Siddiqi, S. M. Fortune, D. B. Moody, and E. J. Rubin. 2009. “Mycobacterial Esx-3 Is Required for Mycobactin-Mediated Iron Acquisition.” Proceedings of the National Academy of Sciences 106 (44): 18792–97. https://doi.org/10.1073/pnas.0900589106.0027-84240744-28311091-6490http://nrs.harvard.edu/urn-3:HUL.InstRepos:41552043The 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.en-USJournal Article2019-10-1510.1073/pnas.0900589106