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Investigation of carbohydrate transport and metabolism in mycobacteria
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Karlikowska, Magdalena (2020) Investigation of carbohydrate transport and metabolism in mycobacteria. PhD thesis, University of Warwick.
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WRAP_Theses_Karlikowska_2020.pdf - Submitted Version Embargoed item. Restricted access to Repository staff only until 22 January 2024. Contact author directly, specifying your specific needs. - Requires a PDF viewer. Download (223Mb) |
Official URL: http://webcat.warwick.ac.uk/record=b3736688
Abstract
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB) which remains one of the most difficult infectious diseases to control in the world. Mtb possesses a low number of carbohydrate transporters: four ATP-binding cassette (ABC) importers and one major facilitator superfamily permease, potentially reflecting the poor nutrient availability inside the host. This study aimed to elucidate the physiological function of three of these putative sugar transporters (UspABC, UgpABCE and SugI) and a sugar metabolism enzyme (NagA) in the model organism Mycobacterium smegmatis and the human pathogen Mtb.
M. smegmatis was used as the host strain for heterologous overexpression and characterisation of Mtb_uspC and Mtb_uspABC. Furthermore, gene knockout mutants were generated in M. smegmatis for the uspC, uspABC and nagA genes and in Mtb for the nagA, sugI and ugpABCE genes. The mutant strains were subjected to phenotypic (via Biolog microarrays), transcriptomic (via RNA-sequencing) and proteomic (via mass spectrometry) analyses to elucidate global quantitative differences between each mutant and the wild type strains. Combined, the results indicated that UspABC is an importer of hexose-phosphates, SugI and NagA have an important role in amino sugar biosynthesis and UgpABCE is associated with import of a phosphate source and, separately, with fatty acid elongation.
Taken together, the findings presented here provide novel insights into the physiological role of nutrient acquisition by Mtb. This knowledge of nutrient import has the potential to inform future TB diagnostics and treatment.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QH Natural history Q Science > QP Physiology Q Science > QR Microbiology |
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Library of Congress Subject Headings (LCSH): | Tuberculosis, Mycobacterium tuberculosis, Mycobacterium tuberculosis -- Genetic aspects, Carbohydrates -- Metabolism, Biological transport | ||||
Official Date: | June 2020 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | School of Life Sciences | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Fullam, Elizabeth ; Besra, Gurdyal | ||||
Sponsors: | Midlands Integrative Biosciences Training Partnership ; Biotechnology and Biological Sciences Research Council (Great Britain) | ||||
Format of File: | |||||
Extent: | xlii, 401 leaves : illustrations | ||||
Language: | eng |
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