Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of <italic toggle="yes">Mycobacterium tuberculosis</italic> MazF Toxins

ABSTRACT mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "extracellular death factors" (EDFs). When secreted from bacterial cultu...

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Autores principales: Akanksha Nigam, Sathish Kumar, Hanna Engelberg-Kulka
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Publicado: American Society for Microbiology 2018
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spelling oai:doaj.org-article:cf46194c78fe48788e488bdc82d029a92021-11-15T16:00:26ZQuorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of <italic toggle="yes">Mycobacterium tuberculosis</italic> MazF Toxins10.1128/mBio.00685-182150-7511https://doaj.org/article/cf46194c78fe48788e488bdc82d029a92018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00685-18https://doaj.org/toc/2150-7511ABSTRACT mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "extracellular death factors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of Escherichia coli MazF. Mycobacterium tuberculosis carries several mazEF modules. Among them, the endoribonucleolytic activities of MazF proteins mt-1, mt-3, and mt-6 were identified. MazF-mt6 and MazF-mt-3 cleave M. tuberculosis rRNAs. Here we report the in vitro effects of EDFs on the endoribonucleolytic activities of M. tuberculosis MazFs. Escherichia coli EDF (EcEDF) and the three Pseudomonas aeruginosa EDFs (PaEDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3 and overcome the inhibitory effect of MazE-mt3 or MazE-mt6 on the endoribonucleolytic activities of the respective toxins. We propose that these EDFs can serve as a basis for a novel class of antibiotics against M. tuberculosis. IMPORTANCE Mycobacterium tuberculosis is one of the leading causes of death from infectious disease. M. tuberculosis is highly drug resistant, and drug delivery to the infected site is very difficult. In previous studies, we showed that extracellular death factors (EDFs) can work as quorum sensing molecules which participate in interspecies bacterial cell death. In this study, we demonstrated the role of different EDFs in the endoribonucleolytic activities of M. tuberculosis MazFs. Escherichia coli EDF (EcEDF) and the three Pseudomonas aeruginosa EDFs (PaEDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3. The current report provides a basis for the use of the EDF peptides EcEDF and PaEDF as novel antibiotics against M. tuberculosis.Akanksha NigamSathish KumarHanna Engelberg-KulkaAmerican Society for Microbiologyarticleextracellular death peptidesMycobacterium tuberculosisquorum sensingMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution DOAJ
collection DOAJ
language EN
topic extracellular death peptides
Mycobacterium tuberculosis
quorum sensing
Microbiology
QR1-502
spellingShingle extracellular death peptides
Mycobacterium tuberculosis
quorum sensing
Microbiology
QR1-502
Akanksha Nigam
Sathish Kumar
Hanna Engelberg-Kulka
Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of <italic toggle="yes">Mycobacterium tuberculosis</italic> MazF Toxins
description ABSTRACT mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "extracellular death factors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of Escherichia coli MazF. Mycobacterium tuberculosis carries several mazEF modules. Among them, the endoribonucleolytic activities of MazF proteins mt-1, mt-3, and mt-6 were identified. MazF-mt6 and MazF-mt-3 cleave M. tuberculosis rRNAs. Here we report the in vitro effects of EDFs on the endoribonucleolytic activities of M. tuberculosis MazFs. Escherichia coli EDF (EcEDF) and the three Pseudomonas aeruginosa EDFs (PaEDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3 and overcome the inhibitory effect of MazE-mt3 or MazE-mt6 on the endoribonucleolytic activities of the respective toxins. We propose that these EDFs can serve as a basis for a novel class of antibiotics against M. tuberculosis. IMPORTANCE Mycobacterium tuberculosis is one of the leading causes of death from infectious disease. M. tuberculosis is highly drug resistant, and drug delivery to the infected site is very difficult. In previous studies, we showed that extracellular death factors (EDFs) can work as quorum sensing molecules which participate in interspecies bacterial cell death. In this study, we demonstrated the role of different EDFs in the endoribonucleolytic activities of M. tuberculosis MazFs. Escherichia coli EDF (EcEDF) and the three Pseudomonas aeruginosa EDFs (PaEDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3. The current report provides a basis for the use of the EDF peptides EcEDF and PaEDF as novel antibiotics against M. tuberculosis.
format article
author Akanksha Nigam
Sathish Kumar
Hanna Engelberg-Kulka
author_facet Akanksha Nigam
Sathish Kumar
Hanna Engelberg-Kulka
author_sort Akanksha Nigam
title Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of <italic toggle="yes">Mycobacterium tuberculosis</italic> MazF Toxins
title_short Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of <italic toggle="yes">Mycobacterium tuberculosis</italic> MazF Toxins
title_full Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of <italic toggle="yes">Mycobacterium tuberculosis</italic> MazF Toxins
title_fullStr Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of <italic toggle="yes">Mycobacterium tuberculosis</italic> MazF Toxins
title_full_unstemmed Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of <italic toggle="yes">Mycobacterium tuberculosis</italic> MazF Toxins
title_sort quorum sensing extracellular death peptides enhance the endoribonucleolytic activities of <italic toggle="yes">mycobacterium tuberculosis</italic> mazf toxins
publisher American Society for Microbiology
publishDate 2018
url https://doaj.org/article/cf46194c78fe48788e488bdc82d029a9
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AT hannaengelbergkulka quorumsensingextracellulardeathpeptidesenhancetheendoribonucleolyticactivitiesofitalictoggleyesmycobacteriumtuberculosisitalicmazftoxins
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