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

journal contribution
posted on 06.08.2015, 08:21 by Obolbek Turapov, Jessica Loraine, Christopher H. Jenkins, P. Barthe, Daniel McFeely, F. Forti, D. Ghisotti, D. Hesek, M. Lee, Andrew R. Bottrill, W. Vollmer, S. Mobashery, M. Cohen-Gonsaud, Galina V. Mukamolova
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.

History

Citation

Open Biology, 2015, 5 (7)

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

Open Biology

Publisher

Royal Society, The: Open Access

eissn

2046-2441

Acceptance date

05/06/2015

Copyright date

2015

Available date

06/08/2015

Publisher version

http://rsob.royalsocietypublishing.org/content/5/7/150025

Language

en