Understanding the genomic information of mycobacterium tuberculosis causing whole genome sequencing approach / Nur Azwin Ismail

Mycobacterium tuberculosis (MTB) causes serious disease of tuberculosis which threatens the world with 8 million individuals infected and 2 million deaths reported each year. MTB spreads by aerosol and infects the host through the lungs. This bacillus is phagocytised by macrophages in the lungs and...

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Main Author: Ismail, Nur Azwin
Format: Thesis
Language:English
Published: 2015
Subjects:
Online Access:http://ir.uitm.edu.my/id/eprint/15849/
http://ir.uitm.edu.my/id/eprint/15849/1/TM_NUR%20AZWIN%20ISMAIL%20PH%2015_5.pdf
id uitm-15849
recordtype eprints
spelling uitm-158492016-12-16T07:40:16Z http://ir.uitm.edu.my/id/eprint/15849/ Understanding the genomic information of mycobacterium tuberculosis causing whole genome sequencing approach / Nur Azwin Ismail Ismail, Nur Azwin biogeochemistry Toxicity testing Mycobacterium tuberculosis (MTB) causes serious disease of tuberculosis which threatens the world with 8 million individuals infected and 2 million deaths reported each year. MTB spreads by aerosol and infects the host through the lungs. This bacillus is phagocytised by macrophages in the lungs and replicate inside these cells. It invades through the macrophage by inhibiting the fusion between phagosome and bactericidal lysosome. The primary macrophage infection results in a proinflammatory response followed by recruitment of other cells that are essentials for the innate and adaptive immune systems. It is known that MTB most commonly affects the lungs. However, it has emerged as an extrapulmonary pathogen that infects any organ system inside the human body. The bacterium is capable of infecting other organ system due to dissemination via lympho-haematogenous route in the early period of the pulmonary infection. A few tuberculosis cases were reported to occur at extrapulmonary sites especially among the immunocomprised. Despite the increase in extrapulmonary TB cases, the mechanisms by which the bacterium subvert host defense mechanism and invade deeper tissue of extrapulmonary site are still poorly understood. Compounding to this lack of knowledge, we therefore use whole genome sequencing platform to complete the genome sequence of extrapulmonary TB strain PR05. With the combination of genomics and bioinformatics analysis, study on the genes essential for virulence and pathogenesis of complete genome sequence of extrapulmonary TB strain PR05 was performed. Based on the annotation of the DNA sequence, proteins function, cellular localization and molecular features were predicted. All the identified genes that are essential for virulence and pathogenesis were grouped into eight categories. Few genes were identified to play role in invasion, and adhesion of extrapulmonary dissemination: erp, fbp, mce and hbhA. Two members (ESX-1 and ESX-5) of MTB unique secretion system, type seven secretion systems (T7SS) was found to be involved in the virulence of M. tuberculosis which affects cell to cell migration of this pathogenic mycobacterium. En route in looking for variations, a comparative analysis between extrapulmonary TB strain and five Pulmonary TB strain was performed to identify the similarities and differences between these strains. The comparative analysis and multiple genome alignment have identified few inversion rearrangement and eleven insertion region encoding 31 genes that play roles in pathogenicity and virulence of MTB. However, current project was not able to pinpoint the exact mechanism causing tropism. Further investigate on the functional importance of genetic variation identified in the extrapulmonary TB strain PR05 is required for better understanding in the mechanism of tropism for extrapulmonary tuberculosis. 2015 Thesis NonPeerReviewed text en http://ir.uitm.edu.my/id/eprint/15849/1/TM_NUR%20AZWIN%20ISMAIL%20PH%2015_5.pdf Ismail, Nur Azwin (2015) Understanding the genomic information of mycobacterium tuberculosis causing whole genome sequencing approach / Nur Azwin Ismail. Masters thesis, Universiti Teknologi MARA.
repository_type Digital Repository
institution_category Local University
institution Universiti Teknologi MARA
building UiTM Institutional Repository
collection Online Access
language English
topic biogeochemistry
Toxicity testing
spellingShingle biogeochemistry
Toxicity testing
Ismail, Nur Azwin
Understanding the genomic information of mycobacterium tuberculosis causing whole genome sequencing approach / Nur Azwin Ismail
description Mycobacterium tuberculosis (MTB) causes serious disease of tuberculosis which threatens the world with 8 million individuals infected and 2 million deaths reported each year. MTB spreads by aerosol and infects the host through the lungs. This bacillus is phagocytised by macrophages in the lungs and replicate inside these cells. It invades through the macrophage by inhibiting the fusion between phagosome and bactericidal lysosome. The primary macrophage infection results in a proinflammatory response followed by recruitment of other cells that are essentials for the innate and adaptive immune systems. It is known that MTB most commonly affects the lungs. However, it has emerged as an extrapulmonary pathogen that infects any organ system inside the human body. The bacterium is capable of infecting other organ system due to dissemination via lympho-haematogenous route in the early period of the pulmonary infection. A few tuberculosis cases were reported to occur at extrapulmonary sites especially among the immunocomprised. Despite the increase in extrapulmonary TB cases, the mechanisms by which the bacterium subvert host defense mechanism and invade deeper tissue of extrapulmonary site are still poorly understood. Compounding to this lack of knowledge, we therefore use whole genome sequencing platform to complete the genome sequence of extrapulmonary TB strain PR05. With the combination of genomics and bioinformatics analysis, study on the genes essential for virulence and pathogenesis of complete genome sequence of extrapulmonary TB strain PR05 was performed. Based on the annotation of the DNA sequence, proteins function, cellular localization and molecular features were predicted. All the identified genes that are essential for virulence and pathogenesis were grouped into eight categories. Few genes were identified to play role in invasion, and adhesion of extrapulmonary dissemination: erp, fbp, mce and hbhA. Two members (ESX-1 and ESX-5) of MTB unique secretion system, type seven secretion systems (T7SS) was found to be involved in the virulence of M. tuberculosis which affects cell to cell migration of this pathogenic mycobacterium. En route in looking for variations, a comparative analysis between extrapulmonary TB strain and five Pulmonary TB strain was performed to identify the similarities and differences between these strains. The comparative analysis and multiple genome alignment have identified few inversion rearrangement and eleven insertion region encoding 31 genes that play roles in pathogenicity and virulence of MTB. However, current project was not able to pinpoint the exact mechanism causing tropism. Further investigate on the functional importance of genetic variation identified in the extrapulmonary TB strain PR05 is required for better understanding in the mechanism of tropism for extrapulmonary tuberculosis.
format Thesis
author Ismail, Nur Azwin
author_facet Ismail, Nur Azwin
author_sort Ismail, Nur Azwin
title Understanding the genomic information of mycobacterium tuberculosis causing whole genome sequencing approach / Nur Azwin Ismail
title_short Understanding the genomic information of mycobacterium tuberculosis causing whole genome sequencing approach / Nur Azwin Ismail
title_full Understanding the genomic information of mycobacterium tuberculosis causing whole genome sequencing approach / Nur Azwin Ismail
title_fullStr Understanding the genomic information of mycobacterium tuberculosis causing whole genome sequencing approach / Nur Azwin Ismail
title_full_unstemmed Understanding the genomic information of mycobacterium tuberculosis causing whole genome sequencing approach / Nur Azwin Ismail
title_sort understanding the genomic information of mycobacterium tuberculosis causing whole genome sequencing approach / nur azwin ismail
publishDate 2015
url http://ir.uitm.edu.my/id/eprint/15849/
http://ir.uitm.edu.my/id/eprint/15849/1/TM_NUR%20AZWIN%20ISMAIL%20PH%2015_5.pdf
first_indexed 2023-09-18T22:54:47Z
last_indexed 2023-09-18T22:54:47Z
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