The following is a summary of “Exploring inter-regulatory gene network derived candidate genes imparting resistance in mycobacterium tuberculosis,” published in the May 2024 issue of Infectious Disease by Naeem et al.
The intricate network of Mycobacterium tuberculosis (Mtb) genes complicates understanding of how drug resistance arises, posing a significant obstacle to global TB elimination by 2030.
Researchers conducted a retrospective study analyzing protein-protein and protein-DNA interactions in Mtb to identify candidate genes potentially linked to drug resistance against first-line anti-TB medications.
They conducted bioinformatic analysis of genome-wide regulator-DNA interactions (Zeng et al., 2012) and global protein-protein interactions (Wang et al., 2010) using Cytoscape software. Which helped identify candidate genes involved in drug resistance networks. The genes were amplified, cloned, and transformed into Mtb-competent cells to create strains overexpressing the respective genes or enhanced green fluorescent protein (eGFP). The strains were then screened with isoniazid (INH) and rifampicin (RIF) to assess their contribution to drug resistance regulation. Resistance was indicated by changes in Alamar blue dye coloration.
The results showed that 30 candidate genes were identified and classified into small molecule metabolism, intermediate metabolism, information pathway, conserved hypothetical proteins, and cell wall-cell processes using mycrobrowser. Exposure to various concentrations of INH and RIF revealed that only 7 strains (Rv3416, Rv1267, Rv0165c, Rv1129c, Rv2669, Rv2703, and Rv2780) displayed resistance, growing in the presence of 200 µg/ml INH without a change in Alamar blue color. No growth change or color alteration was observed against RIF. Findings suggested that these genes potentially regulate the drug resistance network in Mtb.
Investigators concluded that understanding the network of drug resistance mechanisms should be a key focus in developing new anti-TB drugs.
Source: sciencedirect.com/science/article/pii/S1201971223001480
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