UNCOVERING KEY GENES LINKED TO DRUG RESISTANCE THROUGH TRANSCRIPTOMIC ANALYSES AND GENOMIC VARIATION IN MDR AND XDR STRAINS OF MYCOBACTERIUM TUBERCULOSIS

Abstract

The rise of extensively drug-resistant Mycobacterium tuberculosis (XDR-MTB) poses a serious global health threat, which emphasizes the need for understanding the molecular mechanisms behind multidrug-resistant Mycobacterium tuberculosis (MDR-MTB). This study integrates transcriptome sequencing data to explore genomic variations and transcriptomic profiles in XDR and MDR strains. Using available datasets from NCBI and ENA, quality checks, trimming, and performed comparative genome analysis against a reference genome using the Windows Subsystem for Linux (WSL), and key gene variants unique to MDR and XDR strains were identified using the Galaxy tool. The analysis focused on differentially expressed genes that drive resistance mechanisms. Using WSL and RStudio for transcriptomic analysis, critical regulatory elements, such as non coding RNAs, were uncovered that significantly influence bacterial persistence and virulence. These regulatory RNAs enhance the bacterium's ability to survive in hostile conditions, enabling drug resistance. Differential gene expression analysis further revealed overexpression of non-coding RNA RVnc0024 (Mcr7) and small regulatory RNA RVnc0036a (MTS2823) in the regulation of virulence pathways, shedding light on the complex mechanisms fueling resistance. These discoveries not only elevate our understanding of drug resistance in Mycobacterium tuberculosis but also enable the development of targeted therapeutic strategies. By dissecting these molecular intricacies, this study lays the groundwork for innovative interventions aimed at combating one of the world's most pressing public health crises.