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The Mycobacterium tuberculosis relBE toxin:antitoxin genes are stress-responsive modules that regulate growth through translation inhibition

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
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An Erratum to this article was published on 02 December 2015

Abstract

Toxin-antitoxin (TA) genes are ubiquitous among bacteria and are associated with persistence and dormancy. Following exposure to unfavorable environmental stimuli, several species (Escherichia coli, Staphylococcus aureus, Myxococcus xanthus) employ toxin proteins such as RelE and MazF to downregulate growth or initiate cell death. Mycobacterium tuberculosis possesses three Rel TA modules (Rel Mtb ): RelBE Mtb , RelFG Mtb and RelJK Mtb (Rv1246c-Rv1247c, Rv2865-Rv2866, and Rv3357-Rv3358, respectively), which inhibit mycobacterial growth when the toxin gene (relE, relG, relK) is expressed independently of the antitoxin gene (relB, relF, relJ). In the present study, we examined the in vivo mechanism of the RelE Mtb toxin protein, the impact of RelE Mtb on M. tuberculosis physiology and the environmental conditions that regulate all three rel Mtb modules. RelE Mtb negatively impacts growth and the structural integrity of the mycobacterial envelope, generating cells with aberrant forms that are prone to extensive aggregation. At a time coincident with growth defects, RelE Mtb mediates mRNA degradation in vivo resulting in significant changes to the proteome. We establish that rel Mtb modules are stress responsive, as all three operons are transcriptionally activated following mycobacterial exposure to oxidative stress or nitrogen-limiting growth environments. Here we present evidence that the rel Mtb toxin:antitoxin family is stress-responsive and, through the degradation of mRNA, the RelE Mtb toxin influences the growth, proteome and morphology of mycobacterial cells.

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  1. Center for Infectious Diseases and Vaccinology, Biodesign Institute, Arizona State University, Tempe, Arizona, 85287, USA

    Shaleen B. Korch, Vandana Malhotra, Heidi Contreras & Josephine E. Clark-Curtiss

  2. Department of Pharmacology, Midwestern University, Glendale, Arizona, 85308, USA

    Shaleen B. Korch

  3. School of Life Sciences, Arizona State University, Tempe, Arizona, 85287, USA

    Josephine E. Clark-Curtiss

  4. Department of Molecular Biology and Biochemistry, University of California, Irvine, California, 92697, USA

    Heidi Contreras

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Korch, S.B., Malhotra, V., Contreras, H. et al. The Mycobacterium tuberculosis relBE toxin:antitoxin genes are stress-responsive modules that regulate growth through translation inhibition. J Microbiol. 53, 783–795 (2015). https://doi.org/10.1007/s12275-015-5333-8

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