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The development of carbohydrate tools to understand nutrient uptake and metabolism in mycobacteria
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Grypioti, Maria (2021) The development of carbohydrate tools to understand nutrient uptake and metabolism in mycobacteria. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3765527
Abstract
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB). TB is the leading cause of death worldwide from a single-infectious agent, with 1.5 million deaths in 2018. Mtb can persist in the human host in a latent state for decades, and has evolved specialised mechanisms for long term intracellular survival. However, the nutrients that are available to Mtb intracellularly during infection are not fully understood.
Trehalose, a non-mammalian disaccharide, has been shown to play a key role in the survival and virulence of Mtb. It can be found in the Mtb cytoplasm, and within the cell envelope. Understanding of trehalose uptake and metabolism by mycobacteria may lead to development of new therapeutic pathways.
In this Thesis we have employed a chemical biology approach to develop tools to understand the fate of trehalose in mycobacteria. A novel modular chemical probe was designed that incorporates trehalose as ‘bait’ for the enrichment and identification of the mycobacterial proteins that specifically interact with this Mtb disaccharide. A new synthetic methodology was developed and preliminary pull-down experiments using model proteins was conducted. Trehalose was also conjugated onto polymer-stabilised gold nanoparticles to exploit their colorimetric (red to blue) transitions upon aggregation as a detection tool. Quantum dot (QD) nanoparticles were also used as they can be a useful bioimaging tool due to their fluorescent properties. A series of gold and QD nanoparticles conjugated with either glucose or trehalose were synthesized and used to investigate specific binding to lectins and mycobacteria. The AuNPs gave colorimetric responses to lectins, but weaker responses to mycobacteria. Electron microscopy suggested some bacteria interactions. Conjugated QDs were found to bind to M. smegmatis non-specifically.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QC Physics Q Science > QH Natural history Q Science > QR Microbiology T Technology > TP Chemical technology |
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Library of Congress Subject Headings (LCSH): | Mycobacterium tuberculosis, Trehalose, Quantum dots, Carbohydrates -- Metabolism, Biological transport | ||||
Official Date: | March 2021 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | School of Life Sciences | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Gibson, Mathew I. ; Fullam, Elizabeth | ||||
Format of File: | |||||
Extent: | xxiv, 204 leaves : illustrations, map | ||||
Language: | eng |
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