23S rRNA as an a-Maz-ing new bacterial toxin target

Jason M. Schifano, Nancy A. Woychik

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis in humans, is a bacterium with the unique ability to persist for years or decades as a latent infection. This latent state, during which bacteria have a markedly altered physiology and are thought to be dormant, is crucial for the bacteria to survive the stressful environments it encounters in the human host. Importantly, M. tuberculosis cells in the dormant state are generally refractory to antibiotics, most of which target cellular processes occurring in actively replicating bacteria. The molecular switches that enable M. tuberculosis to slow or stop its replication and become dormant remain unknown. However, the slow growth and dormant state that are hallmarks of latent tuberculosis infection have striking parallels to the "quasi-dormant" state of Escherichia coli cells caused by the toxin components of chromosomal toxin-antitoxin (TA) modules. An unusually large number of TA modules in M. tuberculosis, including nine in the mazEF family, may contribute to initiating this latent state or to adapting to stress conditions in the host. Toward filling the gap in our understanding of the physiological role of TA modules in M. tuberculosis, we are interested in identifying their molecular mechanisms to better understand how toxins impart growth control. Our recent publication1 uncovered a novel function of a MazF toxin in M. tuberculosis that had not been associated with any other MazF ortholog. This toxin, MazF-mt6, can disrupt protein synthesis by cleavage of 23S rRNA at a single location in an evolutionarily conserved five-base sequence in the ribosome active center.

Original languageEnglish (US)
Pages (from-to)101-105
Number of pages5
JournalRNA Biology
Volume11
Issue number2
DOIs
StatePublished - Feb 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Keywords

  • Antitoxin
  • Endoribonuclease
  • Protein synthesis
  • Ribosome
  • Tuberculosis

Fingerprint

Dive into the research topics of '23S rRNA as an a-Maz-ing new bacterial toxin target'. Together they form a unique fingerprint.

Cite this