Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages

Journal of Experimental Medicine - Tập 198 Số 5 - Trang 693-704 - 2003
Dirk Schnappinger1,2, Sabine Ehrt1, Martin I. Voskuil3, Yang Liu3, Joseph A. Mangan4, Irene M. Monahan4, Gregory Dolganov5, Brad Efron6, Philip D. Butcher4, Carl Nathan1,2,7, Gary K. Schoolnik3
13Department of Microbiology and Immunology, Weill Medical College and Graduate Programs in
24Molecular Biology, Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021
31Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford Medical School
46Department of Medical Microbiology, St. George's Hospital Medical School, London SW17 ORE, United Kingdom
57Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, CA 94143
62Department of Health Research and Policy, Stanford University, Stanford, CA 94305
75Immunology, Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021

Tóm tắt

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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Thông tin
Thông tin xuất bản

Journal of Experimental Medicine

Tập 198 Số 5

693-704

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