Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition.
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.
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
M Sloan
MS
Siegrist
Meera
M
Unnikrishnan
Matthew J
MJ
McConnell
Mark
M
Borowsky
Tan-Yun
TY
Cheng
Noman
N
Siddiqi
Sarah M
SM
Fortune
D Branch
DB
Moody
Eric J
EJ
Rubin
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016680:Genome, Bacterial / Q000235:genetics; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D009154:Mutation / Q000235:genetics; D009161:Mycobacterium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D009164:Mycobacterium Infections / Q000382:microbiology; D010080:Oxazoles / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D055571:Secretory Pathway / Q000187:drug effects; D017262:Siderophores / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D001426:Bacterial Proteins; D010080:Oxazoles; D017262:Siderophores; C018608:mycobactins; D007501:Iron