Two-Component System Transcriptional Regulator PrrA & Transcriptional Regulator KdpE Revealed as Novel Drug Targets in the Pan-Proteome Analysis of Mycobacterium tuberculosis CCDC5180

Multidrug-resistant bacteria are now widely recognized as a global threat and a substantial public health concern. Antimicrobial resistance (AMR) is known as a more significant threat to humanity. Multidrug-resistant (MDR)/ Extensively Drug-resistant (XDR) Mycobacterium tuberculosis (M. tb) is a prime example of AMR. Furthermore, treating MDR-TB is more challenging since it demands second-line treatments, which have severe side effects. Genomic & proteomic approaches are employed in pharmaceutical research to identify novel drug targets. A subtractive proteomics approach was applied in this study to identify promising therapeutic targets for the MDR strain M. tb CCDC5180. The subtractive proteome approach of the whole proteome of M. tb CCDC5180 showed a list of 14 essential, cytoplasmic, and unique metabolic proteins discovered to be druggable. Among these 14, only eight proteins were involved in the pathogen's virulence. Finally, two proteins, PrrA and KdpE, were identified as potential novel drug targets, and further docking of these proteins with phytochemicals resulted in two promising compounds Cepharanthine and Alianthone against these novel targets.