Kurthkoti, K;
Amin, H;
Marakalala, MJ;
Ghanny, S;
Subbian, S;
Sakatos, A;
Livny, J;
... Rodriguez, GM; + view all
(2017)
The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas.
mBio
, 8
(4)
, Article e01092-17. 10.1128/mBio.01092-17.
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Abstract
This study was conducted to investigate the role of iron deprivation in the persistence of Mycobacterium tuberculosis. We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation M. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of M. tuberculosis under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants. M. tuberculosis mutants compromised in their ability to survive Fe starvation were identified. The findings of this study advance the understanding of the physiological settings that may underpin the chronicity of human tuberculosis (TB) and are relevant to the design of effective antitubercular therapies.
| Type: | Article |
|---|---|
| Title: | The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1128/mBio.01092-17 |
| Publisher version: | https://doi.org/10.1128/mBio.01092-17 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Microbiology, Mycobacterium tuberculosis, TB granuloma, iron acquisition, iron deprivation, iron sequestration, latent TB, nutritional immunity, persistence, GENE-EXPRESSION, HOST-DEFENSE, CONTAINING PHAGOSOMES, TRANSCRIPTION FACTOR, HYPOXIC RESPONSE, EARLY ENDOSOMES, INFECTION, VIRULENCE, GROWTH, BIOSYNTHESIS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10070017 |
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