The cell wall of Mycobacteriumtuberculosis has a very complex ultrastructure, consisting of mycolic acids, an array of polysaccharides and surface exposed antigenic glycolipids. These cell wall components play a vital role in pathogenicity and virulence and hence, are attractive drug targets. Recent advances in TB drug discovery have produced a plethora of candidate drug molecules, many of them, affect mycolic acid biosynthesis and transport.
A major part of the thesis work consists of biochemical and structural characterisation of proteins involved in mycolic acids biosynthesis and transport using a combination of genetic and biophysical tools. Through deletion of fabH, its non-essentiality for growth and survival of mycobacteria was demonstrated, and suggested the possibility of a functional substitute.
The latter part of the thesis deals with the identification and characterisation of glycosyltransferases involved in the biosynthesis of lipooligosaccharides (LOS) in M.kansasii. LOS’s are surface exposed, highly polar antigenic glycolipids, present in several mycobacterial species. Using targeted gene deletion, mutant strain defective in LOS production was obtained that has provided the first insights into LOS biosynthesis in M. \(kansasii.\
