c-di-AMP hydrolysis by the phosphodiesterase AtaC promotes differentiation of multicellular bacteria

authored by: Andreas Latoscha, David Jan Drexler, Mahmoud M Al-Bassam, Adrian M Bandera, Volkhard Kaever, Kim C Findlay, Gregor Witte, Natalia Tschowri
Abstract: Antibiotic-producing Streptomyces use the diadenylate cyclase DisA to synthesize the nucleotide second messenger c-di-AMP, but the mechanism for terminating c-di-AMP signaling and the proteins that bind the molecule to effect signal transduction are unknown. Here, we identify the AtaC protein as a c-di-AMP-specific phosphodiesterase that is also conserved in pathogens such as Streptococcus pneumoniae and Mycobacterium tuberculosis AtaC is monomeric in solution and binds Mn2+ to specifically hydrolyze c-di-AMP to AMP via the intermediate 5'-pApA. As an effector of c-di-AMP signaling, we characterize the RCK_C domain protein CpeA. c-di-AMP promotes interaction between CpeA and the predicted cation/proton antiporter, CpeB, linking c-di-AMP signaling to ion homeostasis in Actinobacteria. Hydrolysis of c-di-AMP is critical for normal growth and differentiation in Streptomyces, connecting ionic stress to development. Thus, we present the discovery of two components of c-di-AMP signaling in bacteria and show that precise control of this second messenger is essential for ion balance and coordinated development in Streptomyces.
External Organisation(s): University of California at San Diego
Humboldt-Universität zu Berlin (HU Berlin)
John Innes Centre
Hannover Medical School (MHH)
Ludwig-Maximilians-Universität München (LMU)
Type: Article
Journal: Proceedings of the National Academy of Sciences of the United States of America
Volume: 117
Pages: 7392-7400
No. of pages: 9
ISSN: 0027-8424
Publication date: 31.03.2020
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: General
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1073/pnas.1917080117 (Access: Unknown)
https://doi.org/10.1073/pnas.2014953117 (Access: Closed)