Cited by 1,420Tuberculosis Research and EpidemiologyMycobacterium research and diagnosisBacterial Genetics and Biotechnology

The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.

Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages

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Abstract

Little is known about the biochemical environment in phagosomes harboring an infectious agent. To assess the state of this organelle we captured the transcriptional responses of Mycobacterium tuberculosis (MTB) in macrophages from wild-type and nitric oxide (NO) synthase 2–deficient mice before and after immunologic activation. The intraphagosomal transcriptome was compared with the transcriptome of MTB in standard broth culture and during growth in diverse conditions designed to simulate features of the phagosomal environment. Genes expressed differentially as a consequence of intraphagosomal residence included an interferon γ– and NO-induced response that intensifies an iron-scavenging program, converts the microbe from aerobic to anaerobic respiration, and induces a dormancy regulon. Induction of genes involved in the activation and β-oxidation of fatty acids indicated that fatty acids furnish carbon and energy. Induction of σE-dependent, sodium dodecyl sulfate–regulated genes and genes involved in mycolic acid modification pointed to damage and repair of the cell envelope. Sentinel genes within the intraphagosomal transcriptome were induced similarly by MTB in the lungs of mice. The microbial transcriptome thus served as a bioprobe of the MTB phagosomal environment, showing it to be nitrosative, oxidative, functionally hypoxic, carbohydrate poor, and capable of perturbing the pathogen's cell envelope.

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  1. 1997, Microbiol. Mol. Biol. Rev., 61, 136

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Metadata

Authors
Schnappinger, D., Ehrt, S., Voskuil, M. I., Liu, Y., Mangan, J. A., Monahan, I. M., Dolganov, G., Efron, B., Butcher, P. D., Nathan, C., & Schoolnik, G. K.
Affiliations
  • Cornell University (US)
  • 3Department of Microbiology and Immunology, Weill Medical College and Graduate Programs in
  • Stanford Medicine (US)
  • St George's, University of London (GB)
  • University of California, San Francisco (US)
  • Stanford University (US)
Corresponding author
Schnappinger, Dirk
Venue
The Journal of Experimental Medicine
Published
2003-09-01
Volume
198
Issue
5
Pages
693-704
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2007097682
Cited by
1,420
References
58
Citations by year
2026: 26 · 2025: 35 · 2024: 46 · 2023: 32 · 2022: 55 · 2021: 41 · 2020: 37 · 2019: 68 · 2018: 63 · 2017: 65 · 2016: 61 · 2015: 96 · 2014: 90 · 2013: 75 · 2012: 96
FWCI
31.28
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • St George's Online Research Archive (St George's University of London) (acceptedVersion)
Funders
  • Hearst Foundations
  • Deutsche Forschungsgemeinschaft
  • National Institutes of Health
  • Defense Advanced Research Projects Agency
  • Advanced Research Projects Agency
  • Medical Research Council
  • National Heart, Lung, and Blood Institute (R01HL068525, HL 61241, HL68525, R01HL061241)
  • National Institute of Allergy and Infectious Diseases (R01AI044826, AI-44826)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
Mycobacterium tuberculosis, macrophages, nitric oxide synthase 2, interferon-gamma, iron scavenging, anaerobic respiration, fatty acid beta-oxidation, sigma E, cell envelope damage, hypoxia, nitrosative stress, tuberculosis pathogenesis
MeSH terms
Animals, Macrophages, Mycobacterium tuberculosis, Phagosomes, RNA, Bacterial, Transcription, Genetic, Gene Expression Regulation, Bacterial, Mice

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