Development of Mycobacterium Tuberculosis Ribosomal RNA as a Drug Target

Abstract

Ribonucleic Acid (RNA) is an important drug or biochemical probe target. (i) For every protein, a drug target is coded for by an RNA that could equally be targeted; (ii) many pathogenic organisms including viruses have RNA genomes that could be potentially targeted. (iii) it is now well established that many new generation antibiotics are targeted at ribosomes which are effective drug targets to treat bacterial infections. Despite the critical role that RNA plays in biology and thus as a potential therapeutic and chemical biology target, only a small number of RNA drug targets have been developed and exploited. The objective of this study was thus to develop rational methods to exploit Mycobacterium tuberculosis RNA as a drug target. To accomplish this objective, we developed a method to isolate and label Mycobacteria tuberculosis ribosomal Ribonucleic Acid (rRNA) transcripts, as well as a study design for identifying all small molecules, or drugs, that bind the RNA with high affinity and specificity developed. This study has enabled the development of an rRNA probe that can be used for screening potential small molecules that target Tuberculosis (TB) rRNA. The long term goal is to develop a RNA motif-ligand database that can be mined against RNA sequences to rationally design small molecules that specifically target RNAs. This study showed that it is possible to target antibiotics to certain RNA structures. This was evident from the colour development that showed that there are sites on RNA that participate in specific interactions with antibiotics.