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Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of Mycobacterium tuberculosis

Akanksha Nigam1, Sathish Kumar1, Hanna Engelberg-Kulka2

  • 1Department of Microbiology and Molecular Genetics, IMRIC, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Mbio
|May 3, 2018
PubMed

Insights

Extracellular death factors (EDFs) from E. coli and P. aeruginosa enhance Mycobacterium tuberculosis MazF toxin activity. These EDFs may form the basis for new antibiotics against drug-resistant tuberculosis.

Area of Science:

  • Bacteriology and Molecular Biology
  • Antimicrobial Drug Discovery

Background:

  • The mazEF toxin-antitoxin system is crucial for bacterial survival and regulation.
  • Extracellular death factors (EDFs) are quorum sensing peptides that induce interspecies cell death and modulate MazF activity.

Purpose of the Study:

  • To investigate the effect of specific EDFs on the endoribonucleolytic activity of Mycobacterium tuberculosis MazF proteins.
  • To explore the potential of EDFs as a novel therapeutic strategy against M. tuberculosis.

Main Methods:

  • In vitro characterization of the endoribonucleolytic activities of M. tuberculosis MazF-mt3 and MazF-mt6.
  • Assay of the effects of Escherichia coli EDF (EcEDF) and Pseudomonas aeruginosa EDFs (PaEDFs) on MazF-mt3 and MazF-mt6 activity.
  • Evaluation of EDFs' ability to counteract MazE antitoxin inhibition.

Main Results:

  • EcEDF and PaEDFs individually enhanced the endoribonucleolytic activities of M. tuberculosis MazF-mt6 and MazF-mt3.
  • EDFs overcame the inhibitory effects of MazE-mt3 and MazE-mt6 on their respective MazF toxins.
  • MazF-mt6 and MazF-mt3 were confirmed to cleave M. tuberculosis rRNAs.

Conclusions:

  • EDFs significantly modulate the activity of M. tuberculosis MazF toxins.
  • The findings support the development of EDFs as a novel class of antibiotics targeting M. tuberculosis.
Keywords:
Mycobacterium tuberculosisextracellular death peptidesquorum sensing

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