Mycobacteria is a genus characterized by its unique layer of mycomembrane, which enhances its pathogenicity causing notorious infections such as tuberculosis or leprosy in humans. Some pathogenic mycobacteria are part of the Mycobacterium tuberculosis complex (MTBC), while others are predominantly environmental and belong to the class of non-tuberculosis mycobacteria (NTM). Some of the NTMs are also opportunistic pathogens causing infections mostly in immunocompromised individuals. In this study, we focus on a recently discovered species of NTM known
as M. riyadhense, originally isolated from a patient with TB-like symptoms in Riyadh. With prepublication access to the completely assembled and fully annotated genomes of M. riyadhense, we wanted to study the gene expression of M. riyadhense after establishing an infection model using a murine macrophage cell line. We performed transcriptomic analysis of M. riyadhense upon infection using RAW264.7 murine macrophages to determine the hallmarks of differentially expressed (DE) genes at early infection time points. Most DE genes observed belong to one of the crucial secretion systems known as ESX-1. Most genes were highly upregulated during 12-hour of infection, particularly esxA and esxB, which encode for ESAT-6 and CFP-10 secretion proteins.
These substrates are essential for the virulence and pathogenicity of Mycobacterium tuberculosis (MTB). In addition, we observed downregulation of WhiB5, a transcriptional regulator that is a well-known controller of Mycobacterium tuberculosis virulence and reactivation, and regulates genes encoding the constituents of two type VII secretion systems, namely, ESX-2 and ESX-4.
We have also identified other genes of yet unknown function that are highly upregulated during early infection needing functional characterization in future follow-up studies. Overall, we have established an in vitro cell infection model for M. riyadhense that can be used to study host pathogen cross talks during infection processes in tubercle bacilli.
|Date of Award||Aug 2019|
|Original language||English (US)|
- Biological, Environmental Sciences and Engineering
|Supervisor||Arnab Pain (Supervisor)|