title: Two DHH subfamily 1 proteins in Streptococcus pneumoniae possess cyclic di-AMP phosphodiesterase activity and affect bacterial growth and virulence.
abstract: Cyclic di-AMP (c-di-AMP) and cyclic di-GMP (c-di-GMP) are signaling molecules that play important roles in bacterial biology and pathogenesis. However, these nucleotides have not been explored in Streptococcus pneumoniae, an important bacterial pathogen. In this study, we characterized the c-di-AMP-associated genes of S. pneumoniae. The results showed that SPD_1392 (DacA) is a diadenylate cyclase that converts ATP to c-di-AMP. Both SPD_2032 (Pde1) and SPD_1153 (Pde2), which belong to the DHH subfamily 1 proteins, displayed c-di-AMP phosphodiesterase activity. Pde1 cleaved c-di-AMP into phosphoadenylyl adenosine (pApA), whereas Pde2 directly hydrolyzed c-di-AMP into AMP. Additionally, Pde2, but not Pde1, degraded pApA into AMP. Our results also demonstrated that both Pde1 and Pde2 played roles in bacterial growth, resistance to UV treatment, and virulence in a mouse pneumonia model. These results indicate that c-di-AMP homeostasis is essential for pneumococcal biology and disease.
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: Leslie E
authors.initials: LE
authors.lastname: Eisele
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Underwood
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Koestler
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Waters
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
authors.forename: Guangchun
authors.initials: G
authors.lastname: Bai
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D011018:Pneumonia, Pneumococcal / Q000382:microbiology / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D015226:Dinucleoside Phosphates; D037521:Virulence Factors; C528998:cyclic diadenosine phosphate; D015105:3',5'-Cyclic-AMP Phosphodiesterases