title: Too much of a good thing: regulated depletion of c-di-AMP in the bacterial cytoplasm.
abstract: Bacteria that synthesize c-di-AMP also encode several mechanisms for controlling c-di-AMP levels within the cytoplasm. One major class of phosphodiesterases comprises GdpP and DhhP homologs, which degrade c-di-AMP into the linear molecule 5'-pApA or AMP by the DHH-DHHA1 domain. The other major class comprises PgpH homologs, which degrade c-di-AMP by the HD domain. Both GdpP and PgpH harbor sensory domains, likely to regulate c-di-AMP hydrolysis activity in response to signal input. As another possible mechanism for controlling cytoplasmic c-di-AMP levels, bacteria also secrete c-di-AMP via multidrug resistance transporters, as demonstrated for Listeria monocytogenes. Mutants that accumulate high c-di-AMP levels, by deletion of phosphodiesterases or multidrug resistance transporters, exhibit aberrant physiology, growth defects, and attenuated virulence in infection.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, WA, United States.
authors.forename: TuAnh Ngoc
authors.initials: TN
authors.lastname: Huynh
authors.affiliation: Department of Microbiology, University of Washington, Seattle, WA, United States. Electronic address: jjwoodwa@uw.edu.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Woodward
mesh_terms: D001419:Bacteria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015226:Dinucleoside Phosphates; C528998:cyclic diadenosine phosphate; D010727:Phosphoric Diester Hydrolases