title: Cyclic di-AMP impairs potassium uptake mediated by a cyclic di-AMP binding protein in Streptococcus pneumoniae.
abstract: Cyclic di-AMP (c-di-AMP) has been shown to play important roles as a second messenger in bacterial physiology and infections. However, understanding of how the signal is transduced is still limited. Previously, we have characterized a diadenylate cyclase and two c-di-AMP phosphodiesterases in Streptococcus pneumoniae, a Gram-positive pathogen. In this study, we identified a c-di-AMP binding protein (CabP) in S. pneumoniae using c-di-AMP affinity chromatography. We demonstrated that CabP specifically bound c-di-AMP and that this interaction could not be interrupted by competition with other nucleotides, including ATP, cAMP, AMP, phosphoadenylyl adenosine (pApA), and cyclic di-GMP (c-di-GMP). By using a bacterial two-hybrid system and genetic mutagenesis, we showed that CabP directly interacted with a potassium transporter (SPD_0076) and that both proteins were required for pneumococcal growth in media with low concentrations of potassium. Interestingly, the interaction between CabP and SPD_0076 and the efficiency of potassium uptake were impaired by elevated c-di-AMP in pneumococci. These results establish a direct c-di-AMP-mediated signaling pathway that regulates pneumococcal potassium uptake.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA.
authors.forename: Yinlan
authors.initials: Y
authors.lastname: Bai
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Zarrella
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
authors.forename: Guangchun
authors.initials: G
authors.lastname: Bai
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D015226:Dinucleoside Phosphates / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D011188:Potassium / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D015226:Dinucleoside Phosphates; C528998:cyclic diadenosine phosphate; D011188:Potassium