Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages
By D. Schnappinger, S. Ehrt, M. Voskuil, Yang Liu, J. Mangan, I. Monahan, G. Dolganov, Bradley Efron, P. Butcher, C. Nathan and 1 more. Journal of Experimental Medicine, 2003
1,006 citations recorded by the source corpus.
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.
Subfields: Epidemiology, Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/e7475528b421f89ae807e1d03f7f9a82f1ae93cd
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Citations in the corpus
- Interpreting Expression Data with Metabolic Flux Models: Predicting Mycobacterium tuberculosis Mycolic Acid Production (2009, background): “Bacterial metabolism plays an important role in TB pathology, both in terms of metabolic alterations associated with intracellular growth [9–12] as well as through the production of metabolic products associated with virulence – including mycolic acids [13–15].”
- Mycobacterium tuberculosis: Success through dormancy (2012, background): “Genome-wide microarray techniques to study Mtb’s transcriptional response to this transition have provided deeper insights into the nature of the phagosomal environment, which was suggested to be nitrosative, oxidative, low in oxygen tension, and limited in nutrients (Schnappinger et al., 2003).”
- Macrophage defense mechanisms against intracellular bacteria (2015, background): “5)P2] and PI(3,4,5)P3 participate in phagocytic cup formation and enclosure, probably in synergy with the SNAREs, VAMP3, and VAMP7, otherwise associated with recycling endosomes or exocytosis, respectively.”