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Activation of the glmS Ribozyme Confers Bacterial Growth Inhibition
Author(s) -
Schüller Anna,
Matzner Daniel,
Lünse Christina E.,
Wittmann Valentin,
Schumacher Catherine,
Unsleber Sandra,
BrötzOesterhelt Heike,
Mayer Christoph,
Bierbaum Gabriele,
Mayer Günter
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600491
Subject(s) - ribozyme , prodrug , mechanism of action , mechanism (biology) , in vivo , antibacterial activity , biology , bacteria , mode of action , chemistry , computational biology , microbiology and biotechnology , biochemistry , in vitro , rna , genetics , philosophy , epistemology , gene
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.