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Article

Cyclic Di-adenosine Monophosphate Regulates Metabolism and Growth in the Oral Commensal Streptococcus mitis

1
Institute of Oral Biology, University of Oslo, 0316 Oslo, Norway
2
Norwegian Veterinary Institute, Pb 750 Sentrum, 0106 Oslo, Norway
*
Author to whom correspondence should be addressed.
These authors contributed equally to the study.
Microorganisms 2020, 8(9), 1269; https://doi.org/10.3390/microorganisms8091269
Received: 18 July 2020 / Revised: 14 August 2020 / Accepted: 18 August 2020 / Published: 20 August 2020
(This article belongs to the Section Molecular Microbiology and Immunology)
Cyclic di-adenosine monophosphate (c-di-AMP) has emerged as an important bacterial signaling molecule that functions both as an intracellular second messenger in bacterial cells and an extracellular ligand involved in bacteria-host cross-talk. In this study, we identify and characterize proteins involved in controlling the c-di-AMP concentration in the oral commensal and opportunistic pathogen Streptococcusmitis (S. mitis). We identified three known types of c-di-AMP turnover proteins in the genome of S. mitis CCUG31611: a CdaA-type diadenylate cyclase as well as GdpP-, and DhhP-type phosphodiesterases. Biochemical analyses of purified proteins demonstrated that CdaA synthesizes c-di-AMP from ATP whereas both phosphodiesterases can utilize c-di-AMP as well as the intermediary metabolite of c-di-AMP hydrolysis 5′-phosphadenylyl-adenosine (pApA) as substrate to generate AMP, albeit at different catalytic efficiency. Using deletion mutants of each of the genes encoding c-di-AMP turnover proteins, we show by high resolution MS/MS that the intracellular concentration of c-di-AMP is increased in deletion mutants of the phosphodiesterases and non-detectable in the cdaA-mutant. We also detected pApA in mutants of the DhhP-type phosphodiesterase. Low and high levels of c-di-AMP were associated with longer and shorter chains of S. mitis, respectively indicating a role in regulation of cell division. The deletion mutant of the DhhP-type phosphodiesterase displayed slow growth and reduced rate of glucose metabolism. View Full-Text
Keywords: Streptococcus mitis; c-di-AMP; diadenylate cyclase; phosphodiesterase; growth; metabolism Streptococcus mitis; c-di-AMP; diadenylate cyclase; phosphodiesterase; growth; metabolism
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MDPI and ACS Style

Rørvik, G.H.; Liskiewicz, K.A.; Kryuchkov, F.; Naemi, A.-O.; Aasheim, H.-C.; Petersen, F.C.; Küntziger, T.M.; Simm, R. Cyclic Di-adenosine Monophosphate Regulates Metabolism and Growth in the Oral Commensal Streptococcus mitis. Microorganisms 2020, 8, 1269. https://doi.org/10.3390/microorganisms8091269

AMA Style

Rørvik GH, Liskiewicz KA, Kryuchkov F, Naemi A-O, Aasheim H-C, Petersen FC, Küntziger TM, Simm R. Cyclic Di-adenosine Monophosphate Regulates Metabolism and Growth in the Oral Commensal Streptococcus mitis. Microorganisms. 2020; 8(9):1269. https://doi.org/10.3390/microorganisms8091269

Chicago/Turabian Style

Rørvik, Gro H., Krystyna A. Liskiewicz, Fedor Kryuchkov, Ali-Oddin Naemi, Hans-Christian Aasheim, Fernanda C. Petersen, Thomas M. Küntziger, and Roger Simm. 2020. "Cyclic Di-adenosine Monophosphate Regulates Metabolism and Growth in the Oral Commensal Streptococcus mitis" Microorganisms 8, no. 9: 1269. https://doi.org/10.3390/microorganisms8091269

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