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J Mol Biol. 2019 Jan 19. pii: S0022-2836(19)30012-9. doi: 10.1016/j.jmb.2019.01.014. [Epub ahead of print]

Recent Advances and Current Trends in Nucleotide Second Messenger Signaling in Bacteria.

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Institute of Biology/Microbiology, Humboldt-Universität zu Berlin, 10115 Berlin, Germany. Electronic address:
Institute of Molecular Bacteriology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; Institute of Molecular Bacteriology, TWINCORE GmbH, Center for Clinical and Experimental Infection Research, 30625 Hannover, Germany.
Institute of Biology/Microbiology, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.
Department of General Microbiology, Institute of Microbiology and Genetics, Georg-August-Universität Göttingen, 37077 Göttingen, Germany.
Institute of Microbiology, Leibniz-Universität Hannover, 30419 Hannover, Germany.


The "International Symposium on Nucleotide Second Messenger Signaling in Bacteria" (September 30-October 3, 2018, Berlin), which was organized within the framework of DFG Priority Programme 1879 (, brought together 125 participants from 20 countries to discuss recent progress and future trends in this field. Even 50 years after its discovery, (p)ppGpp is venturing into exciting new fields, especially in gram-positive bacteria. After triggering the current renaissance in bacterial second messenger research, c-di-GMP is becoming ever more global with abounding new molecular mechanisms of action and physiological functions. The more recently discovered c-di-AMP is rapidly catching up and has now been found even in archaea, with its function in osmotic homeostasis being conserved across kingdom boundaries. Small modules associated with mobile genetic elements, which make and react to numerous novel mixed cyclic dinucleotides, seem to roam around rather freely in the bacterial world. Finally, many novel and old nucleotide molecules are still lurking around in search of a function. Across many talks it became apparent that (p)ppGpp, c-di-GMP and GTP/ATP can share and compete for binding sites (e.g., the Walker A motif in GTP/ATPases) with intriguing regulatory consequences, thus contributing to the emergent trend of systemwide networks that interconnect diverse signaling nucleotides. Overall, this inspiring conference made it clear that second messenger signaling is currently one of the most dynamic and exciting areas in microbial molecular biology and physiology, with major impacts ranging from microbial systems biology and ecology to infection biology.


biofilm; c-di-AMP; c-di-GMP; cGAMP; ppGpp


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