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Front Microbiol. 2017 Jul 13;8:1328. doi: 10.3389/fmicb.2017.01328. eCollection 2017.

Identification of the Components Involved in Cyclic Di-AMP Signaling in Mycoplasma pneumoniae.

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Department of General Microbiology, Institute of Microbiology and Genetics, Georg-August University GöttingenGöttingen, Germany.
Research Core Unit Metabolomics, Hannover Medical SchoolHannover, Germany.
Biolog Life Science InstituteBremen, Germany.
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine GreifswaldGreifswald, Germany.


Bacteria often use cyclic dinucleotides as second messengers for signal transduction. While the classical molecule c-di-GMP is involved in lifestyle selection, the functions of the more recently discovered signaling nucleotide cyclic di-AMP are less defined. For many Gram-positive bacteria, c-di-AMP is essential for growth suggesting its involvement in a key cellular function. We have analyzed c-di-AMP signaling in the genome-reduced pathogenic bacterium Mycoplasma pneumoniae. Our results demonstrate that these bacteria produce c-di-AMP, and we could identify the diadenylate cyclase CdaM (MPN244). This enzyme is the founding member of a novel family of diadenylate cyclases. Of two potential c-di-AMP degrading phosphodiesterases, only PdeM (MPN549) is active in c-di-AMP degradation, whereas NrnA (MPN140) was reported to degrade short oligoribonucleotides. As observed in other bacteria, both the c-di-AMP synthesizing and the degrading enzymes are essential for M. pneumoniae suggesting control of a major homeostatic process. To obtain more insights into the nature of this process, we have identified a c-di-AMP-binding protein from M. pneumoniae, KtrC. KtrC is the cytoplasmic regulatory subunit of the low affinity potassium transporter KtrCD. It is established that binding of c-di-AMP inhibits the KtrCD activity resulting in a limitation of potassium uptake. Our results suggest that the control of potassium homeostasis is the essential function of c-di-AMP in M. pneumoniae.


Mollicutes; c-di-AMP; diadenylate cyclase; phosphodiesterase; potassium uptake; second messenger

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