Genome-wide bioinformatics analysis of FMN, SAM-I, glmS, TPP, lysine, purine, cobalamin, and SAH riboswitches for their applications as allosteric antibacterial drug targets in human pathogenic bacteria

Expert Opin Ther Targets. 2019 Jul;23(7):631-643. doi: 10.1080/14728222.2019.1618274. Epub 2019 May 14.

Abstract

Objectives: A constantly growing number of antibiotic-resistant strains of human pathogenic bacteria is an acute problem. Prolonged illnesses and increasing mortality worldwide mean that there is an urgent need to develop novel antibacterial drugs based on new targets and mechanisms of action. We present in silico analyses of bacterial riboswitches that may be suitable as antibacterial drug targets. Methods: Most bacterial riboswitches are allosteric cis-acting gene control elements located in the 5'-untranslated region of messenger RNAs. Riboswitches sense specific metabolites and regulate the synthesis of some essential cellular metabolites in many pathogenic bacteria but are not found in humans. We present a complete and comprehensive genome-wide bioinformatics analyses of the suitability of eight riboswitches as antibacterial drug targets in various pathogenic bacteria. Results: Based on our in silico analyses, we classify the riboswitches in four different groups based on their suitability to be used as antibacterial drug targets. We have estimated that FMN, SAM-I, glmS, TPP, and Lysine riboswitches are promising targets for antibacterial drug discovery. Conclusion: This research enables us to focus antibacterial drug discovery research only on those riboswitches whose inhibition will result in suppression of the growth of certain pathogenic bacteria.

Keywords: Antibacterial drug discovery; allosteric drug targets; bacterial riboswitches; biochemical pathways; bioinformatics analysis; human bacterial pathogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Computational Biology*
  • Computer Simulation
  • Drug Design
  • Drug Discovery*
  • Genome-Wide Association Study
  • Humans
  • Riboswitch / genetics

Substances

  • Anti-Bacterial Agents
  • Riboswitch