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MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs

Author

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  • Prabhakar Tiwari

    (Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute)

  • Garima Arora

    (Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute)

  • Mamta Singh

    (Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute)

  • Saqib Kidwai

    (Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute)

  • Om Prakash Narayan

    (Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute)

  • Ramandeep Singh

    (Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute)

Abstract

Toxin–antitoxin (TA) systems are highly conserved in members of the Mycobacterium tuberculosis (Mtb) complex and have been proposed to play an important role in physiology and virulence. Nine of these TA systems belong to the mazEF family, encoding the intracellular MazF toxin and its antitoxin, MazE. By overexpressing each of the nine putative MazF homologues in Mycobacterium bovis BCG, here we show that Rv1102c (MazF3), Rv1991c (MazF6) and Rv2801c (MazF9) induce bacteriostasis. The construction of various single-, double- and triple-mutant Mtb strains reveals that these MazF ribonucleases contribute synergistically to the ability of Mtb to adapt to conditions such as oxidative stress, nutrient depletion and drug exposure. Moreover, guinea pigs infected with the triple-mutant strain exhibits significantly reduced bacterial loads and pathological damage in infected tissues in comparison with parental strain-infected guinea pigs. The present study highlights the importance of MazF ribonucleases in Mtb stress adaptation, drug tolerance and virulence.

Suggested Citation

  • Prabhakar Tiwari & Garima Arora & Mamta Singh & Saqib Kidwai & Om Prakash Narayan & Ramandeep Singh, 2015. "MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7059
    DOI: 10.1038/ncomms7059
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    Cited by:

    1. Moise Mansour & Emmanuel Giudice & Xibing Xu & Hatice Akarsu & Patricia Bordes & Valérie Guillet & Donna-Joe Bigot & Nawel Slama & Gaetano D’urso & Sophie Chat & Peter Redder & Laurent Falquet & Lione, 2022. "Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Xibing Xu & Ben Usher & Claude Gutierrez & Roland Barriot & Tom J. Arrowsmith & Xue Han & Peter Redder & Olivier Neyrolles & Tim R. Blower & Pierre Genevaux, 2023. "MenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Tannu Priya Gosain & Saurabh Chugh & Zaigham Abbas Rizvi & Neeraj Kumar Chauhan & Saqib Kidwai & Krishan Gopal Thakur & Amit Awasthi & Ramandeep Singh, 2024. "Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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