Open Biology (Jan 2015)

The external PASTA domain of the essential serine/threonine protein kinase PknB regulates mycobacterial growth

  • Obolbek Turapov,
  • Jessica Loraine,
  • Christopher H. Jenkins,
  • Philippe Barthe,
  • Daniel McFeely,
  • Francesca Forti,
  • Daniela Ghisotti,
  • Dusan Hesek,
  • Mijoon Lee,
  • Andrew R. Bottrill,
  • Waldemar Vollmer,
  • Shahriar Mobashery,
  • Martin Cohen-Gonsaud,
  • Galina V. Mukamolova

DOI
https://doi.org/10.1098/rsob.150025
Journal volume & issue
Vol. 5, no. 7

Abstract

Read online

PknB is an essential serine/threonine protein kinase required for mycobacterial cell division and cell-wall biosynthesis. Here we demonstrate that overexpression of the external PknB_PASTA domain in mycobacteria results in delayed regrowth, accumulation of elongated bacteria and increased sensitivity to β-lactam antibiotics. These changes are accompanied by altered production of certain enzymes involved in cell-wall biosynthesis as revealed by proteomics studies. The growth inhibition caused by overexpression of the PknB_PASTA domain is completely abolished by enhanced concentration of magnesium ions, but not muropeptides. Finally, we show that the addition of recombinant PASTA domain could prevent regrowth of Mycobacterium tuberculosis, and therefore offers an alternative opportunity to control replication of this pathogen. These results suggest that the PknB_PASTA domain is involved in regulation of peptidoglycan biosynthesis and maintenance of cell-wall architecture.

Keywords