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.
|Date of Award||Apr 2014|
|Original language||English (US)|
- Biological, Environmental Science and Engineering
|Supervisor||Arnab Pain (Supervisor)|