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Title: Role of lsp a gene in the biology and pathogenesis of mycobacterium tuberculosis
Researcher: Pathak, Rakesh
Guide(s): Bose, Mridula
Saluja, Daman
Keywords: Microbiology
Upload Date: 3-Dec-2013
University: University of Delhi
Completed Date: 2012
Abstract: In Mycobacterium tuberculosis, there is only a single gene (Rv1539) that encodes for LspA (Signal peptidase) protein. There are more than 104 lipoproteins in M. tuberculosis that are matured by signal peptidase activity of LspA. Many of these lipoproteins have been reported as virulence factors for M. tuberculosis. Therefore the lspA gene turns out to be very attractive target to develop newer therapeutics to combat tuberculosis. In an attempt to understand the role of lspA gene in the biology and pathogenesis of M .tuberculosis, the lspAgene was cloned in a suitable vector and the protein was expressed and purified to raise polyclonal antibody in rabbit. The lspA gene was also overexpressed in M. tuberculosis H37Rv (M.tb:lspAand#8593;).Overexpression of lspA gene enhanced the in-vitro growth of M. tuberculosis. Electron microscopy showed enhanced thickness of M.tb:lspAand#8593;strain. Immunogoldexperiments demonstrate accumulation of LspA coated particles along the cell wall of strain. Furtherwork demonstrates enhanced resistance to first line antitubercular drugs too. By using aerosol route of infection and mouse model it has been shown here that the overexpression of the gene (lspA) makes the M. tuberculosisstrain more pathogenic and induces a strong immunogenic effect that leads to Th1 type of immune response. Furthermore, in silico analysis revealed that the lspAgene is a constitutively expressed gene that lies in an operon with Rv1540. This observation has been experimentally confirmed here. It has also been demonstrated here that the lspA gene is constitutively expressed and regulated by a strong promoter. Taken together the present study establishes the biological relevance of the lspA gene on a firm footing. We propose this may prove to be a good drug target to combat tuberculosis in the years to come.
Pagination: vi,151p.
Appears in Departments:Dept. of Microbiology

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01_title.pdfAttached File58.13 kBAdobe PDFView/Open
02_declaration.pdf25.34 kBAdobe PDFView/Open
03_certificate.pdf29.24 kBAdobe PDFView/Open
04_acknowledgement.pdf60.6 kBAdobe PDFView/Open
05_content.pdf70.96 kBAdobe PDFView/Open
06_abbreviations.pdf34.24 kBAdobe PDFView/Open
07_chapter 1.pdf47.89 kBAdobe PDFView/Open
08_chapter 2.pdf541.19 kBAdobe PDFView/Open
09_aims & objectives.pdf40.49 kBAdobe PDFView/Open
10_chapter 3.pdf298.58 kBAdobe PDFView/Open
11_chapter 4.pdf1.12 MBAdobe PDFView/Open
12_chapter 5.pdf1.42 MBAdobe PDFView/Open
13_chapter 6.pdf867.82 kBAdobe PDFView/Open
14_summary & conclusion.pdf56.75 kBAdobe PDFView/Open
15_refrences.pdf115.17 kBAdobe PDFView/Open
16_appendix.pdf61.45 kBAdobe PDFView/Open
17_abstract.pdf73.16 kBAdobe PDFView/Open

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