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

verfasst von

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.

Externe Organisation(en)

University of California at San Diego
Humboldt-Universität zu Berlin (HU Berlin)
John Innes Centre
Medizinische Hochschule Hannover (MHH)
Ludwig-Maximilians-Universität München (LMU)

Typ

Artikel

Journal

Proceedings of the National Academy of Sciences of the United States of America

Band

117

Seiten

7392-7400

Anzahl der Seiten

9

ISSN

0027-8424

Publikationsdatum

31.03.2020

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Allgemein

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1073/pnas.1917080117 (Zugang: Unbekannt)
https://doi.org/10.1073/pnas.2014953117 (Zugang: Geschlossen)