Meta-analysis of active tuberculosis gene expression ascertains host directed drug targets

Abstract

Multi-drug resistant tuberculosis still remains a major public health crisis globally. With the emergence of newer active tuberculosis disease, the requirement of prolonged treatment time and adherence to therapy till its completion necessitates the search of newer therapeutics, targeting human host factors. The current work utilized statistical meta-analysis of human gene transcriptomes of active pulmonary tuberculosis disease obtained from six public datasets. The meta-analysis resulted in the identification of 2038 significantly differentially expressed genes (DEGs) in the active tuberculosis disease. The gene ontology (GO) analysis revealed that these genes were major contributors in immune responses. The pathway enrichment analyses identified from various human canonical pathways are related to other infectious diseases. In addition, the comparison of the DEGs with the tuberculosis genome wide association study (GWAS) datasets revealed the presence of few genetic variants in their proximity. The analysis of protein interaction networks (human and Mycobacterium tuberculosis) and host directed drug-target interaction network led to new candidate drug targets for drug repurposing studies. The current work sheds light on host genes and pathways enriched in active tuberculosis disease and suggest potential drug repurposing targets for host-directed therapies.

High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity

“…It is worth noting that elevated levels of secreted P-gp have been associated with disease severity or therapeutic response failure in conditions such as chronic rhinosinusitis, rheumatoid arthritis, and systemic lupus erythematosus [94][95][96]. ABCB1 is included in a list of 20 differentially expressed genes in whole blood that distinguish patients with active tuberculosis from healthy individuals [97]. Increased expression and functional activity of P-gp have been found in memory CD4 T cells of patients with latent TB compared to non-infected controls [98].…”