Karlikowska, Magdalena (2020) Investigation of carbohydrate transport and metabolism in mycobacteria. PhD thesis, University of Warwick.

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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)
Subjects:	Q Science > QH Natural history Q Science > QP Physiology Q Science > QR Microbiology
Library of Congress Subject Headings (LCSH):	Tuberculosis, Mycobacterium tuberculosis, Mycobacterium tuberculosis -- Genetic aspects, Carbohydrates -- Metabolism, Biological transport
Official Date:	June 2020
Dates:	Date Event June 2020 UNSPECIFIED
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Publication Status:	Unpublished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:	pdf
Extent:	xlii, 401 leaves : illustrations
Language:	eng

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