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dc.contributor.authorRengarajan, Jyothi
dc.contributor.authorBloom, Barry R.
dc.contributor.authorRubin, Eric J.
dc.date.accessioned2019-10-15T18:22:19Z
dc.date.issued2005
dc.identifier.citationRengarajan, J., B. R. Bloom, and E. J. Rubin. 2005. “From The Cover: Genome-Wide Requirements for Mycobacterium Tuberculosis Adaptation and Survival in Macrophages.” Proceedings of the National Academy of Sciences 102 (23): 8327–32. https://doi.org/10.1073/pnas.0503272102.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41552038*
dc.description.abstractMacrophages are central to host defense against microbes, but intracellular pathogens have evolved to evade their antimicrobial functions. Mycobacterium tuberculosis (MTB) has successfully exploited macrophages as its primary niche in vivo, but the bacterial genome-wide requirements that promote its intracellular survival remain undefined. Here we comprehensively identify the MTB genes required for survival by screening for transposon mutants that fail to grow within primary macrophages. We identify mutants showing decreased growth in macrophage environments that model stages of the host immune response. By systematically analyzing several biologically relevant data sets, we have been able to identify putative pathways that could not be predicted by genome organization alone. In one example, phosphate transport, requiring physically unlinked genes, was found to be critical for MTB growth in macrophages and important for establishing persistent infection in lungs. Remarkably, the majority of MTB genes found by this analysis to be required for survival are constitutively expressed rather than regulated by macrophages, revealing the host-adapted lifestyle of an evolutionarily selected intracellular pathogen.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleGenome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages
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.available2019-10-15T18:22:19Z
dash.workflow.comments1Science Serial ID 89786
dc.identifier.doi10.1073/pnas.0503272102
dash.source.volume102;23
dash.source.page8327-8332


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