Zinc regulates a switch between primary and alternative S18 ribosomal proteins in Mycobacterium tuberculosis

Mol Microbiol. 2015 Jul;97(2):263-80. doi: 10.1111/mmi.13022. Epub 2015 May 15.


The Mycobacterium tuberculosis genome encodes five putative 'alternative' ribosomal proteins whose expression is repressed at high Zn(2+) concentration. Each alternative protein has a primary homologue that is predicted to bind Zn(2+). We hypothesized that zinc triggers a switch between these paired homologous proteins and therefore chose one of these pairs, S18-1/S18-2, to study mechanisms of the predicted competition for their incorporation into ribosomes. Our data show that Zn(2+)-depletion causes accumulation of both S18-2 mRNA and protein. In contrast, S18-1 mRNA levels are unchanged to slightly elevated under Zn(2+)-limited conditions. However, the amount of S18-1 protein is markedly decreased. We further demonstrate that both S18 proteins interact with ribosomal protein S6, a committed step in ribosome biogenesis. Zn(2+) is absolutely required for the S18-1/S6 interaction while it is dispensable for S18-2/S6 dimer formation. These data suggest a model in which S18-1 is the dominant ribosome constituent in high zinc conditions, e.g. inside of phagosomes, but that it can be replaced by S18-2 when zinc is deficient, e.g. in the extracellular milieu. Consequently, Zn(2+)-depletion may serve as a signal for building alternative ribosomes when M. tuberculosis is released from macrophages, to allow survival in the extracellular environment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Bacterial
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / metabolism*
  • RNA, Bacterial / biosynthesis*
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism
  • Ribosomal Protein S6 / genetics
  • Ribosomal Protein S6 / metabolism
  • Ribosomal Proteins / biosynthesis
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Zinc / metabolism*


  • RNA, Bacterial
  • RNA, Ribosomal
  • Ribosomal Protein S6
  • Ribosomal Proteins
  • ribosomal protein S18
  • Zinc