Comparative Genomics and Transcriptomic Analysis of Mycobacterium Kansasii

Handle URI:
http://hdl.handle.net/10754/316010
Title:
Comparative Genomics and Transcriptomic Analysis of Mycobacterium Kansasii
Authors:
Alzahid, Yara
Abstract:
The group of Mycobacteria is one of the most intensively studied bacterial taxa, as they cause the two historical and worldwide known diseases: leprosy and tuberculosis. Mycobacteria not identified as tuberculosis or leprosy complex, have been referred to by ‘environmental mycobacteria’ or ‘Nontuberculous mycobacteria (NTM). Mycobacterium kansasii (M. kansasii) is one of the most frequent NTM pathogens, as it causes pulmonary disease in immuno-competent patients and pulmonary, and disseminated disease in patients with various immuno-deficiencies. There have been five documented subtypes of this bacterium, by different molecular typing methods, showing that type I causes tuberculosis-like disease in healthy individuals, and type II in immune-compromised individuals. The remaining types are said to be environmental, thereby, not causing any diseases. The aim of this project was to conduct a comparative genomic study of M. kansasii types I-V and investigating the gene expression level of those types. From various comparative genomics analysis, provided genomics evidence on why M. kansasii type I is considered pathogenic, by focusing on three key elements that are involved in virulence of Mycobacteria: ESX secretion system, Phospholipase c (plcb) and Mammalian cell entry (Mce) operons. The results showed the lack of the espA operon in types II-V, which renders the ESX- 1 operon dysfunctional, as espA is one of the key factors that control this secretion system. However, gene expression analysis showed this operon to be deleted in types II, III and IV. Furthermore, plcB was found to be truncated in types III and IV. Analysis of Mce operons (1-4) show that mce-1 operon is duplicated, mce-2 is absent and mce-3 and mce-4 is present in one copy in M. kansasii types I-V. Gene expression profiles of type I-IV, showed that the secreted proteins of ESX-1 were slightly upregulated in types II-IV when compared to type I and the secreted forms of ESX-5 were highly down regulated in the same types. Differentially expressed genes in types II-IV were also evaluated and validated by qPCR for selected genes. This study gave a general view of the genome of this bacterium and its types, highlighted some different aspects of its subtypes and supplemented by gene expression data.
Advisors:
Pain, Arnab ( 0000-0002-1755-2819 )
Committee Member:
Gehring, Christoph A ( 0000-0003-4355-4591 ) ; Ravasi, Timothy ( 0000-0002-9950-465X )
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Program:
Bioscience
Issue Date:
Apr-2014
Type:
Thesis
Appears in Collections:
Bioscience Program; Theses; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.advisorPain, Arnaben
dc.contributor.authorAlzahid, Yaraen
dc.date.accessioned2014-04-20T07:33:16Z-
dc.date.available2014-04-20T07:33:16Z-
dc.date.issued2014-04en
dc.identifier.urihttp://hdl.handle.net/10754/316010en
dc.description.abstractThe group of Mycobacteria is one of the most intensively studied bacterial taxa, as they cause the two historical and worldwide known diseases: leprosy and tuberculosis. Mycobacteria not identified as tuberculosis or leprosy complex, have been referred to by ‘environmental mycobacteria’ or ‘Nontuberculous mycobacteria (NTM). Mycobacterium kansasii (M. kansasii) is one of the most frequent NTM pathogens, as it causes pulmonary disease in immuno-competent patients and pulmonary, and disseminated disease in patients with various immuno-deficiencies. There have been five documented subtypes of this bacterium, by different molecular typing methods, showing that type I causes tuberculosis-like disease in healthy individuals, and type II in immune-compromised individuals. The remaining types are said to be environmental, thereby, not causing any diseases. The aim of this project was to conduct a comparative genomic study of M. kansasii types I-V and investigating the gene expression level of those types. From various comparative genomics analysis, provided genomics evidence on why M. kansasii type I is considered pathogenic, by focusing on three key elements that are involved in virulence of Mycobacteria: ESX secretion system, Phospholipase c (plcb) and Mammalian cell entry (Mce) operons. The results showed the lack of the espA operon in types II-V, which renders the ESX- 1 operon dysfunctional, as espA is one of the key factors that control this secretion system. However, gene expression analysis showed this operon to be deleted in types II, III and IV. Furthermore, plcB was found to be truncated in types III and IV. Analysis of Mce operons (1-4) show that mce-1 operon is duplicated, mce-2 is absent and mce-3 and mce-4 is present in one copy in M. kansasii types I-V. Gene expression profiles of type I-IV, showed that the secreted proteins of ESX-1 were slightly upregulated in types II-IV when compared to type I and the secreted forms of ESX-5 were highly down regulated in the same types. Differentially expressed genes in types II-IV were also evaluated and validated by qPCR for selected genes. This study gave a general view of the genome of this bacterium and its types, highlighted some different aspects of its subtypes and supplemented by gene expression data.en
dc.language.isoenen
dc.subjectComparativeen
dc.subjectGenomicsen
dc.subjectMycobacteriumen
dc.subjectKansaiien
dc.subjectTranscriptomicsen
dc.subjectMycobateriaen
dc.titleComparative Genomics and Transcriptomic Analysis of Mycobacterium Kansasiien
dc.typeThesisen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
thesis.degree.grantorKing Abdullah University of Science and Technologyen_GB
dc.contributor.committeememberGehring, Christoph Aen
dc.contributor.committeememberRavasi, Timothyen
thesis.degree.disciplineBioscienceen
thesis.degree.nameMaster of Scienceen
dc.person.id124286en
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