Title | Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment. |
Publication Type | Journal Article |
Year of Publication | 2003 |
Authors | Schnappinger D, Ehrt S, Voskuil MI, Liu Y, Mangan JA, Monahan IM, Dolganov G, Efron B, Butcher PD, Nathan C, Schoolnik GK |
Journal | J Exp Med |
Volume | 198 |
Issue | 5 |
Pagination | 693-704 |
Date Published | 2003 Sep 01 |
ISSN | 0022-1007 |
Keywords | Animals, Gene Expression Regulation, Bacterial, Macrophages, Mice, Mycobacterium tuberculosis, Phagosomes, RNA, Bacterial, Transcription, Genetic |
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 gamma- 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 beta-oxidation of fatty acids indicated that fatty acids furnish carbon and energy. Induction of sigmaE-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. |
DOI | 10.1084/jem.20030846 |
Alternate Journal | J Exp Med |
PubMed ID | 12953091 |
PubMed Central ID | PMC2194186 |
Grant List | HL 68525 / HL / NHLBI NIH HHS / United States R01 AI044826 / AI / NIAID NIH HHS / United States AI 44826 / AI / NIAID NIH HHS / United States R01 HL068525 / HL / NHLBI NIH HHS / United States HL 61241 / HL / NHLBI NIH HHS / United States |
Submitted by jom4013 on December 3, 2020 - 3:26pm