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Unlabelled: 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.

Importance: 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.

Titel:	Phenotypes Associated with the Essential Diadenylate Cyclase CdaA and Its Potential Regulator CdaR in the Human Pathogen Listeria monocytogenes.
Autor/in / Beteiligte Person:	Rismondo, J ; Gibhardt, J ; Rosenberg, J ; Kaever, V ; Halbedel, S ; Commichau, FM
Zeitschrift:	Journal of bacteriology, Jg. 198 (2015-11-02), Heft 3, S. 416-26
Veröffentlichung:	Washington, DC : American Society for Microbiology, 2015
Medientyp:	academicJournal
ISSN:	1098-5530 (electronic)
DOI:	10.1128/JB.00845-15
Schlagwort:	Bacterial Proteins genetics Cell Membrane genetics Cell Membrane metabolism Cell Wall physiology Gene Deletion Homeostasis Listeria monocytogenes genetics Osmotic Pressure Phosphorus-Oxygen Lyases genetics Protein Transport Bacterial Proteins metabolism Gene Expression Regulation, Bacterial physiology Listeria monocytogenes enzymology Listeria monocytogenes metabolism Phosphorus-Oxygen Lyases metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [J Bacteriol] 2015 Nov 02; Vol. 198 (3), pp. 416-26. <i>Date of Electronic Publication: </i>2015 Nov 02 (<i>Print Publication: </i>2016). MeSH Terms: Bacterial Proteins / metabolism ; Gene Expression Regulation, Bacterial / physiology ; Listeria monocytogenes / enzymology ; Listeria monocytogenes / metabolism ; Phosphorus-Oxygen Lyases / *metabolism ; Bacterial Proteins / genetics ; Cell Membrane / genetics ; Cell Membrane / metabolism ; Cell Wall / physiology ; Gene Deletion ; Homeostasis ; Listeria monocytogenes / genetics ; Osmotic Pressure ; Phosphorus-Oxygen Lyases / genetics ; Protein Transport References: MBio. 2013;4(3):e00018-13. (PMID: 23631912) ; Microbiology. 2013 Jul;159(Pt 7):1390-401. (PMID: 23676438) ; Proc Natl Acad Sci U S A. 2013 May 28;110(22):9084-9. (PMID: 23671116) ; J Biol Chem. 2015 Feb 27;290(9):5826-39. (PMID: 25575594) ; J Biol Chem. 2015 Mar 6;290(10):6596-606. (PMID: 25605729) ; Mol Microbiol. 2015 May;96(4):779-95. (PMID: 25682701) ; Cell Host Microbe. 2015 Jun 10;17(6):788-98. (PMID: 26028365) ; Microbiologyopen. 2015 Jun;4(3):361-74. (PMID: 25693966) ; J Biol Chem. 2015 Jun 26;290(26):16393-402. (PMID: 25957408) ; Mol Microbiol. 2015 Jul;97(2):189-204. (PMID: 25869574) ; J Bacteriol. 2015 Oct;197(20):3265-74. (PMID: 26240071) ; Science. 2001 Oct 26;294(5543):849-52. (PMID: 11679669) ; Nucleic Acids Res. 2004;32(14):e115. (PMID: 15304544) ; Anal Biochem. 1976 May 7;72:248-54. (PMID: 942051) ; Proc Natl Acad Sci U S A. 1998 May 12;95(10):5752-6. (PMID: 9576956) ; Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8916-21. (PMID: 9671779) ; Appl Environ Microbiol. 2004 Nov;70(11):6887-91. (PMID: 15528558) ; BMC Genomics. 2005;6:39. (PMID: 15774001) ; Cell. 2006 May 19;125(4):679-90. (PMID: 16713562) ; Mol Microbiol. 2007 Mar;63(5):1453-67. (PMID: 17302820) ; Microbiology. 2013 Jul;159(Pt 7):1298-300. (PMID: 23704784) ; Mol Microbiol. 2008 May;68(4):1029-46. (PMID: 18363795) ; Nat Rev Microbiol. 2013 Aug;11(8):513-24. (PMID: 23812326) ; PLoS One. 2013;8(7):e69425. (PMID: 23869242) ; PLoS One. 2013;8(8):e73512. (PMID: 24013956) ; Nat Chem Biol. 2013 Dec;9(12):834-9. (PMID: 24141192) ; J Bacteriol. 2014 Feb;196(3):614-23. (PMID: 24272783) ; J Biol Chem. 2014 Jul 25;289(30):21098-107. (PMID: 24939848) ; Cell. 2014 Sep 11;158(6):1389-401. (PMID: 25215494) ; FEBS Lett. 2015 Jan 2;589(1):45-51. (PMID: 25435171) ; Mol Microbiol. 2015 Jan;95(2):332-51. (PMID: 25424554) ; J Biol Chem. 2015 Jan 30;290(5):3069-80. (PMID: 25433025) ; J Biol Chem. 2015 Jan 30;290(5):2888-901. (PMID: 25505271) ; DNA Repair (Amst). 2015 Mar;27:1-8. (PMID: 25616256) ; Mol Cell. 2008 Apr 25;30(2):167-78. (PMID: 18439896) ; Appl Environ Microbiol. 2008 Jul;74(13):3921-34. (PMID: 18441118) ; Nature. 2009 Jun 18;459(7249):950-6. (PMID: 19448609) ; Science. 2010 Jun 25;328(5986):1703-5. (PMID: 20508090) ; Protein Sci. 2011 Feb;20(2):396-405. (PMID: 21154411) ; EMBO Rep. 2011 Jun;12(6):594-601. (PMID: 21566650) ; PLoS Pathog. 2011 Sep;7(9):e1002217. (PMID: 21909268) ; Nat Methods. 2011;8(10):785-6. (PMID: 21959131) ; Mol Microbiol. 2012 Feb;83(3):623-39. (PMID: 22211522) ; Mol Microbiol. 2012 Feb;83(4):821-39. (PMID: 22353466) ; Science. 2012 Mar 2;335(6072):1103-6. (PMID: 22383849) ; PLoS One. 2012;7(8):e42982. (PMID: 22912771) ; J Biol Chem. 2013 Jan 18;288(3):2004-17. (PMID: 23192352) ; J Biol Chem. 2013 Feb 1;288(5):3085-96. (PMID: 23250743) ; MBio. 2013;4(3):e00282-13. (PMID: 23716572) Substance Nomenclature: 0 (Bacterial Proteins) ; EC 4.6.- (Phosphorus-Oxygen Lyases) Entry Date(s): Date Created: 20151104 Date Completed: 20160531 Latest Revision: 20181113 Update Code: 20240513 PubMed Central ID: PMC4719461

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Phenotypes Associated with the Essential Diadenylate Cyclase CdaA and Its Potential Regulator CdaR in the Human Pathogen Listeria monocytogenes.