title: Osmosensory signaling in Mycobacterium tuberculosis mediated by a eukaryotic-like Ser/Thr protein kinase.
abstract: 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.
authors.affiliation: Departments of Chemistry and Molecular and Cell Biology, California Institute for Quantitative Biosciences (QB3), and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
authors.forename: Stavroula K
authors.initials: SK
authors.lastname: Hatzios
authors.forename: Christina E
authors.initials: CE
authors.lastname: Baer
authors.forename: Tige R
authors.initials: TR
authors.lastname: Rustad
authors.forename: M Sloan
authors.initials: MS
authors.lastname: Siegrist
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Pang
authors.forename: Corrie
authors.initials: C
authors.lastname: Ortega
authors.forename: Tom
authors.initials: T
authors.lastname: Alber
authors.forename: Christoph
authors.initials: C
authors.lastname: Grundner
authors.forename: David R
authors.initials: DR
authors.lastname: Sherman
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Bertozzi
mesh_terms: D000220:Adaptation, Biological / Q000502:physiology*; D015153:Blotting, Western; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D049452:Green Fluorescent Proteins; D046228:Microarray Analysis; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000502:physiology*; D009994:Osmolar Concentration; D009997:Osmotic Pressure / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D049452:Green Fluorescent Proteins; D011494:Protein Kinases; C112455:PknD protein, Nostoc sp. PCC 7120
keywords: environmental sensing; extracellular osmolarity; transcriptional regulation; type VII secretion