Activation of the glmS Ribozyme Confers Bacterial Growth Inhibition

Chembiochem. 2017 Mar 2;18(5):435-440. doi: 10.1002/cbic.201600491. Epub 2017 Jan 30.


The ever-growing number of pathogenic bacteria resistant to treatment with antibiotics call for the development of novel compounds with as-yet unexplored modes of action. Here, we demonstrate the in vivo antibacterial activity of carba-α-d-glucosamine (CGlcN). In this mode of action study, we provide evidence that CGlcN-mediated growth inhibition is due to glmS ribozyme activation, and we demonstrate that CGlcN hijacks an endogenous activation pathway, hence utilizing a prodrug mechanism. This is the first report describing antibacterial activity mediated by activating the self-cleaving properties of a ribozyme. Our results open the path towards a compound class with an entirely novel and distinct molecular mechanism.

Keywords: RNA; antibiotics; hydrolysis; ribozymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacillus subtilis / drug effects*
  • Bacillus subtilis / genetics
  • Bacillus subtilis / growth & development
  • Cyclohexanols / chemistry*
  • Cyclohexylamines / chemistry*
  • Enzyme Activation / drug effects
  • Glucosamine / pharmacology*
  • Microbial Sensitivity Tests
  • Models, Biological
  • Mutation
  • RNA, Catalytic / genetics
  • RNA, Catalytic / metabolism*


  • Anti-Bacterial Agents
  • Cyclohexanols
  • Cyclohexylamines
  • RNA, Catalytic
  • carbaglucosamine
  • Glucosamine