Metabolite-sensing Riboswitches as Antibacterial Drug Targets
Elaine R. Lee, Kenneth F. Blount and Ronald R. Breaker
from: Emerging Trends in Antibacterial Discovery: Answering the Call to Arms (Edited by: Alita A. Miller and Paul F. Miller). Caister Academic Press, U.K. (2011)
The need for new antibacterial drug targets increases as antibiotic resistant pathogens continue to arise. Researchers have recently begun to investigate whether structured noncoding RNAs such as riboswitches can be exploited as targets for new classes of antimicrobial compounds. Riboswitches are gene control elements made entirely of RNA, and in bacteria they are usually located in the 5' untranslated regions (UTRs) of messenger RNAs. These elements are capable of forming complex structures that selectively bind to specific fundamental metabolites and often control the expression of proteins critical for bacterial metabolism and survival. In principle, novel ligands could be designed that target specific riboswitches and alter the expression of the critical genes they regulate. Several riboswitch classes have begun to be examined as potential targets for new classes of antibacterial compounds. Herein we present some of the data generated by efforts to validate riboswitches as drug targets and discuss some of the key unanswered questions that will determine the ultimate success of antibacterial compounds that interact with these RNAs read more ...