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Front. Microbiol. | doi: 10.3389/fmicb.2018.02870

Artificial activation of Escherichia coli mazEF and hipBA toxin-antitoxin systems by antisense peptide nucleic acids as an antibacterial strategy

 Marcin Równicki1, Tomasz Pieńko1, 2,  Jakub Czarnecki3, 4, Monika Kolanowska1, 2,  Dariusz Bartosik3 and  Joanna Trylska1*
  • 1Centre of New Technologies, University of Warsaw, Poland
  • 2Department of Drug Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Poland
  • 3Department of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Poland
  • 4Unit of Bacterial Genome Plasticity, Department of Genomes and Genetics, Institut Pasteur, France

The search for new, non-standard targets is currently a high priority in the design of new antibacterial compounds. Bacterial toxin-antitoxin systems (TAs) are genetic modules that encode a toxin protein that causes growth arrest by interfering with essential cellular processes, and a cognate antitoxin, which neutralizes the toxin activity. TAs have no human analogues, are highly abundant in bacterial genomes, and therefore represent attractive alternative targets for antimicrobial drugs. This study demonstrates how artificial activation of Escherichia coli mazEF and hipBA toxin-antitoxin systems using sequence-specific antisense peptide nucleic acid oligomers is an innovative antibacterial strategy. The growth arrest observed in E. coli resulted from the inhibition of translation of the antitoxins by the antisense oligomers. Furthermore, two other targets, related to the activities of mazEF and hipBA, were identified as promising sites of action for antibacterials. These results show that TAs are susceptible to sequence-specific antisense agents and provide a proof-of-concept for their further exploitation in antimicrobial strategies.

Keywords: bacterial toxin-antitoxin systems, Antimicrobial strategies, Peptide nucleic acid ( PNA ), Escherichia coli mazEF and hipBA targets, antisense oligonucleotides

Received: 13 Sep 2018; Accepted: 08 Nov 2018.

Edited by:

Natalia V. Kirienko, Rice University, United States

Reviewed by:

Chew Chieng Yeo, Sultan Zainal Abidin University, Malaysia
Ilana Kolodkin-Gal, Weizmann Institute of Science, Israel  

Copyright: © 2018 Równicki, Pieńko, Czarnecki, Kolanowska, Bartosik and Trylska. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Joanna Trylska, University of Warsaw, Centre of New Technologies, Warsaw, 00-927, Masovian, Poland, joanna@cent.uw.edu.pl