Mycobacterial glycolipids: pathways to synthesis and role in virulence

1790 15 40587 6 93506 document 40587 Sarkar12PhD.pdf application/pdf a4995017687e195e111b3c352846043a MD5 12448219 2014-12-15 18:57:22 http://etheses.bham.ac.uk//id/eprint/1790/1/Sarkar12PhD.pdf 1790 1 1 application/pdf application/pdf en public

Sarkar12PhD.pdf

http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/40588 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/40588 http://eprints.org/relation/hassmallThumbnailVersion http://etheses.bham.ac.uk/id/document/40588 http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/40589 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/40589 http://eprints.org/relation/haspreviewThumbnailVersion http://etheses.bham.ac.uk/id/document/40589 http://eprints.org/relation/hasVolatileVersion http://etheses.bham.ac.uk/id/document/40590 http://eprints.org/relation/hasVersion http://etheses.bham.ac.uk/id/document/40590 http://eprints.org/relation/hasIndexCodesVersion http://etheses.bham.ac.uk/id/document/40590 40588 2 93514 document 40588 small.png image/png 93b2761daf1ec6bd2fdfa9c6ad15ae53 MD5 3183 2014-12-15 19:07:14 http://etheses.bham.ac.uk//id/eprint/1790/2/small.png 1790 2 2 image/png thumbnail_small Thumbnail Documents conversion from application/pdf to thumbnail_small en staffonly

small.png

preview.jpg

indexcodes.txt

http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/40587 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/40587 http://eprints.org/relation/isIndexCodesVersionOf http://etheses.bham.ac.uk/id/document/40587 archive 4031 disk0/00/00/17/90 2014-12-15 19:06:47 2019-01-23 09:54:52 2014-12-15 19:06:47 thesis show 0 Sarkar Debasmita Besra Gurdyal S. Bhatt Apoorva University of Birmingham Mycobacterial glycolipids: pathways to synthesis and role in virulence unpub QH301 10col_life Mycobacterial diseases are responsible for numerous deaths worldwide, the major pathogens being Mycobacterium tuberculosis and Mycobacterium leprae. Also, in recent years threats from opportunistic pathogens, such as Mycobacterium marinum and Mycobacterium kansasii have been on the rise. These mycobacteria possess a unique lipid-rich cell wall with an array of mycolic acids and species-specific antigenic glycolipids, like the lipooligosaccharides. Some of these solvent extractable lipids possess immunomodulatory properties and play an important role during infection. Lipooligosaccharides (LOS) are surface exposed, polar, antigenic glycolipids that are present in several mycobacterial species. This study used the opportunistic human pathogens M. marinum and M. kansasii as a model system to unravel the genes involved in the biosynthesis of LOSs in Mycobacterium. Using directed mutagenesis and transposon mutagenesis, mutant strains defective in various parts of the LOS biosynthetic pathway were isolated. Analysis of these strains helped in further delineating the pathway and understanding the role of LOSs in virulence. A part of this thesis focussed on studying mycolic acid processing and transport using Mycobacterium smegmatis as a surrogate system. Mycolic acids are the most distinctive components of the mycobacterial cell wall. While their biosynthesis has been studied in detail, processing and transport across the membrane is not well understood. This study attempted to explore the roles of the two putative type II mycolyltransferases MSMEG3437 and MSMEG5851 in mycolic acid processing. Additionally, the role of M. tuberculosis mmpL11 gene was probed as the Mtb-mmpL11 had been reported to be involved in virulence. A null ii mutant of the M. smegmatis homologue, Ms-mmpL11 (MSMEG0241) was generated and analysed for the above study. Deletion mutant strains of the two putative mycolyltransferase II did not show any phenotype, suggesting that their roles are redundant in vivo. Although the Ms-mmpL gene was found to be non-essential, it was found to be involved in transport of free mycolic acids. 2012-07 2012-02 graduation eng author unchecked This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. The Darwin Trust of Edinburgh public 300 University of Birmingham School of Biosciences d_ph other 2012-07 graduation