Osmosensory signaling in Mycobacterium tuberculosis mediated by a eukaryotic-like Ser/Thr protein kinase

Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):E5069-77. doi: 10.1073/pnas.1321205110. Epub 2013 Dec 5.


Bacteria are able to adapt to dramatically different microenvironments, but in many organisms, the signaling pathways, transcriptional programs, and downstream physiological changes involved in adaptation are not well-understood. Here, we discovered that osmotic stress stimulates a signaling network in Mycobacterium tuberculosis regulated by the eukaryotic-like receptor Ser/Thr protein kinase PknD. Expression of the PknD substrate Rv0516c was highly induced by osmotic stress. Furthermore, Rv0516c disruption modified peptidoglycan thickness, enhanced antibiotic resistance, and activated genes in the regulon of the alternative σ-factor SigF. Phosphorylation of Rv0516c regulated the abundance of EspA, a virulence-associated substrate of the type VII ESX-1 secretion system. These findings identify an osmosensory pathway orchestrated by PknD, Rv0516c, and SigF that enables adaptation to osmotic stress through cell wall remodeling and virulence factor production. Given the widespread occurrence of eukaryotic-like Ser/Thr protein kinases in bacteria, these proteins may play a broad role in bacterial osmosensing.

Keywords: environmental sensing; extracellular osmolarity; transcriptional regulation; type VII secretion.

Publication types

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

MeSH terms

  • Adaptation, Biological / physiology*
  • Blotting, Western
  • Gene Expression Regulation, Bacterial / genetics*
  • Green Fluorescent Proteins
  • Microarray Analysis
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / physiology*
  • Osmolar Concentration
  • Osmotic Pressure / physiology*
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Signal Transduction / physiology*


  • Green Fluorescent Proteins
  • Protein Kinases
  • PknD protein, Nostoc sp. PCC 7120

Associated data

  • GEO/GSE50159
  • GEO/GSE50160