Show simple item record

dc.contributor.authorMadigan, Cressida A.
dc.contributor.authorCheng, Tan-Yun
dc.contributor.authorLayre, Emilie
dc.contributor.authorYoung, David C.
dc.contributor.authorMcConnell, Matthew J.
dc.contributor.authorDebono, C. Anthony
dc.contributor.authorMurry, Jeffrey P.
dc.contributor.authorWei, Jun-Rong
dc.contributor.authorBarry, Clifton E. 3rd
dc.contributor.authorRodriguez, G. Marcela
dc.contributor.authorMatsunaga, Isamu
dc.contributor.authorRubin, Eric J.
dc.contributor.authorMoody, D. Branch
dc.date.accessioned2019-10-15T18:22:15Z
dc.date.issued2012
dc.identifier.citationMadigan, C. A., T.-Y. Cheng, E. Layre, D. C. Young, M. J. McConnell, C. A. Debono, J. P. Murry, et al. 2012. “Lipidomic Discovery of Deoxysiderophores Reveals a Revised Mycobactin Biosynthesis Pathway in Mycobacterium Tuberculosis.” Proceedings of the National Academy of Sciences 109 (4): 1257–62. https://doi.org/10.1073/pnas.1109958109.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41552032*
dc.description.abstractTo measure molecular changes underlying pathogen adaptation, we generated a searchable dataset of more than 12,000 mass spectrometry events, corresponding to lipids and small molecules that constitute a lipidome for Mycobacterium tuberculosis. Iron is essential for M. tuberculosis survival, and the organism imports this metal using mycobactin and carboxymycobactin siderophores. Detection of an unexpected siderophore variant and deletions of genes for iron scavenging has led to a revised mycobactin biosynthesis model. An organism-wide search of the M. tuberculosis database for hypothetical compounds predicted by this model led to the discovery of two families of previously unknown lipids, designated monodeoxymycobactins and monodeoxycarboxymycobactins. These molecules suggest a revised biosynthetic model that alters the substrates and order of action of enzymes through the mycobactin biosynthetic pathway. We tested this model genetically by solving M. tuberculosis lipidomes after deletion of the iron-dependent regulator (ideR), mycobactin synthase B (mbtB), or mycobactin synthase G (mbtG). These studies show that deoxymycobactins are actively regulated during iron starvation, and also define essential roles of MbtG in converting deoxymycobactins to mycobactin and in promoting M. tuberculosis growth. Thus, lipidomics is an efficient discovery tool that informs genetic relationships, leading to a revised general model for the biosynthesis of these virulence-conferring siderophores.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleLipidomic discovery of deoxysiderophores reveals a revised mycobactin biosynthesis pathway in Mycobacterium tuberculosis
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorRubin, Eric J.::2ccf3691d766f02c048797e00c06cc44::600
dc.date.available2019-10-15T18:22:15Z
dash.workflow.comments1Science Serial ID 90898
dc.identifier.doi10.1073/pnas.1109958109
dash.source.volume109;4
dash.source.page1257


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record