Tuberculosis (TB) is an infectious disease caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb). During infection, Mtb is continuously exposed to stress from the host immune system. In order to adapt and survive, Mtb counts on its defence mechanisms, which are tightly regulated and rely on rapid adjustments of gene expression in response to external stimuli. Small RNAs (sRNAs) are important regulators of gene expression and play a central role in the adaptation of the bacterium to the different environments encountered throughout its life cycle.
The aims of this thesis were to study the response of Mtb to various forms of infection-related stress (nitrosative, oxidative, alkylative, and DNA damage) and liquid culture supplements at the transcriptomic and proteomic levels, as well as to investigate the presence or absence of sRNAs under these conditions. To this end, we employed high-throughput RNA sequencing (RNA-seq), mass spectrometry, bioinformatics analysis, molecular biology techniques, and genetic tools.
Collectively, the findings of this thesis contribute to a better understanding of the complex responses of Mtb to external stimuli in addition to improving TB diagnostics.