title: Cyclic di-AMP mediates biofilm formation.
abstract: Cyclic di-AMP (c-di-AMP) is an emerging second messenger in bacteria. It has been shown to play important roles in bacterial fitness and virulence. However, transduction of c-di-AMP signaling in bacteria and the role of c-di-AMP in biofilm formation are not well understood. The level of c-di-AMP is modulated by activity of di-adenylyl cyclase that produces c-di-AMP and phosphodiesterase (PDE) that degrades c-di-AMP. In this study, we determined that increased c-di-AMP levels by deletion of the pdeA gene coding for a PDE promoted biofilm formation in Streptococcus mutans. Deletion of pdeA upregulated expression of gtfB, the gene coding for a major glucan producing enzyme. Inactivation of gtfB blocked the increased biofilm by the pdeA mutant. Two c-di-AMP binding proteins including CabPA (SMU_1562) and CabPB (SMU_1708) were identified. Interestingly, only CabPA deficiency inhibited both the increased biofilm formation and the upregulated expression of GtfB observed in the pdeA mutant. In addition, CabPA but not CabPB interacted with VicR, a known transcriptional factor that regulates expression of gtfB, suggesting that a signaling link between CabPA and GtfB through VicR. Increased biofilm by the pdeA deficiency also enhanced bacterial colonization of Drosophila in vivo. Taken together, our studies reveal a new role of c-di-AMP in mediating biofilm formation through a CabPA/VicR/GtfB signaling network in S. mutans.
authors.affiliation: Department of Pediatric Dentistry, University of Alabama at Birmingham, School of Dentistry, Birmingham, AL, USA.|State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Peng
authors.affiliation: Center for Immunology and Microbial Disease, MC-151, Albany Medical College, 47 New Scotland Avenue, Albany, NY, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Immunology and Microbial Disease, MC-151, Albany Medical College, 47 New Scotland Avenue, Albany, NY, USA.
authors.forename: Guangchun
authors.initials: G
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pediatric Dentistry, University of Alabama at Birmingham, School of Dentistry, Birmingham, AL, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D015398:Signal Transduction; D013295:Streptococcus mutans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D015226:Dinucleoside Phosphates; D014157:Transcription Factors; C528998:cyclic diadenosine phosphate; D000249:Adenosine Monophosphate; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP