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MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs
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MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs
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Journal Article
MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs
2015
Overview
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.
Mycobacterium tuberculosis
possesses several toxin–antitoxin systems of the MazEF family. Here, Tiwari
et al
. show that these systems contribute to stress adaptation, antibiotic tolerance and virulence.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 59
/ 64
/ 82
/ 82/80
/ 82/83
/ Animals
/ Antitubercular Agents - chemistry
/ Bacterial Proteins - metabolism
/ Bacterial Proteins - physiology
/ Endoribonucleases - metabolism
/ Endoribonucleases - physiology
/ Female
/ Humanities and Social Sciences
/ Kinetics
/ Mutation
/ Mycobacterium bovis - metabolism
/ Mycobacterium tuberculosis - metabolism
/ Science
/ Swine
/ Toxins
