title: Phenotypes Associated with the Essential Diadenylate Cyclase CdaA and Its Potential Regulator CdaR in the Human Pathogen Listeria monocytogenes.
abstract: Cyclic diadenylate monophosphate (c-di-AMP) is a second messenger utilized by diverse bacteria. In many species, including the Gram-positive human pathogen Listeria monocytogenes, c-di-AMP is essential for growth. Here we show that the single diadenylate cyclase of L. monocytogenes, CdaA, is an integral membrane protein that interacts with its potential regulatory protein, CdaR, via the transmembrane protein domain. The presence of the CdaR protein is not required for the membrane localization and abundance of CdaA. We have also found that CdaR negatively influences CdaA activity in L. monocytogenes and that the role of CdaR is most evident at a high growth temperature. Interestingly, a cdaR mutant strain is less susceptible to lysozyme. Moreover, CdaA contributes to cell division, and cells depleted of CdaA are prone to lysis. The observation that the growth defect of a CdaA depletion strain can be partially restored by increasing the osmolarity of the growth medium suggests that c-di-AMP is important for maintaining the integrity of the protective cell envelope. Overall, this work provides new insights into the relationship between CdaA and CdaR.
  
  
  OBJECTIVE
  Cyclic diadenylate monophosphate (c-di-AMP) is a recently identified second messenger that is utilized by the Gram-positive human pathogen Listeria monocytogenes. Here we show that the single diadenylate cyclase of L. monocytogenes, CdaA, is an integral membrane protein that interacts with CdaR, its potential regulatory protein. We show that CdaR is not required for membrane localization or abundance of the diadenylate cyclase, but modulates its activity. Moreover, CdaA seems to contribute to cell division. Overall, this work provides new insights into the relationship between CdaA and CdaR and their involvement in cell growth.
authors.affiliation: FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany.
authors.forename: Jeanine
authors.initials: J
authors.lastname: Rismondo
authors.affiliation: Department of General Microbiology, Georg August University Göttingen, Göttingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Gibhardt
authors.affiliation: Department of General Microbiology, Georg August University Göttingen, Göttingen, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: Research Core Unit Metabolomics, Hannover Medical School, Hannover, Germany.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.affiliation: FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany halbedels@rki.de fcommic1@gwdg.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Halbedel
authors.affiliation: Department of General Microbiology, Georg August University Göttingen, Göttingen, Germany halbedels@rki.de fcommic1@gwdg.de.
authors.forename: Fabian M
authors.initials: FM
authors.lastname: Commichau
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000502:physiology; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006706:Homeostasis; D008089:Listeria monocytogenes / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D009997:Osmotic Pressure; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D001426:Bacterial Proteins; D019761:Phosphorus-Oxygen Lyases