Year: 2019
Type: article
Abstract: 3',3'-cyclic GMP-AMP (cGAMP) is the third cyclic dinucleotide (CDN) to be discovered in bacteria. No activators of cGAMP signaling have yet been identified, and the signaling pathways for cGAMP have been inferred to display a narrow distribution based upon the characterized synthases, DncV and Hypr GGDEFs. Here, we report that the ubiquitous second messenger cyclic AMP (cAMP) is an activator of the Hypr GGDEF enzyme GacB from Myxococcus xanthus. Furthermore, we show that GacB is inhibited directly by cyclic di-GMP, which provides evidence for cross-regulation between different CDN pathways. Finally, we reveal that the HD-GYP enzyme PmxA is a cGAMP-specific phosphodiesterase (GAP) that promotes resistance to osmotic stress in M. xanthus. A signature amino acid change in PmxA was found to reprogram substrate specificity and was applied to predict the presence of non-canonical HD-GYP phosphodiesterases in many bacterial species, including phyla previously not known to utilize cGAMP signaling.
Source: Molecular Microbiology
DOI: 10.1111/mmi.14412
Authors: Todd A. Wright, Lucy Jiang, James J. Park, Wyatt A. Anderson, Ge Chen, Zachary F. Hallberg, Beiyan Nan, Ming C. Hammond
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: The Origin of Rod Shape in Bacteria, G3993276539, Collaborative Research: A Model for Divergent Bacterial Signaling Networks; Linking New Cyclic Dinucleotides to Environmental and Electrical Lifestyles, Collaborative Research: A Model for Divergent Bacterial Signaling Networks; Linking New Cyclic Dinucleotides to Environmental and Electrical Lifestyles, G7196404773, G9000012003, Enabling High-Throughput Analysis and Single-Cell Imaging of Bacterial Signals
OpenAlex ID: W2982552522